Updated on 2024/03/28

写真a

 
SHIMIZU Kazunori
 
Organization
Graduate School of Engineering Biomolecular Engineering 2 Associate professor
Graduate School
Graduate School of Engineering
Undergraduate School
School of Engineering Chemistry and Biotechnology
Title
Associate professor
Contact information
メールアドレス

Degree 1

  1. 博士(工学) ( 2007.3   名古屋大学 ) 

Research Interests 6

  1. 生物工学

  2. Bio-microsystem

  3. 医用工学

  4. 医用工学

  5. 生物工学

  6. Bio-microsystem

Current Research Project and SDGs 3

  1. Development of in vitro organ/tissue models for drug development and disease research

  2. Development of novel cell culture technologies for use in regenerative medicine and drug development

  3. Screening and development of novel short functional peptides

Research History 13

  1. Associate Professor, Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya Univ. JAPAN

    2017.4

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    Country:Japan

  2. Boston University   Department of Biomedical Engineering   Visiting Researcher

    2018.4 - 2019.2

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    Country:United States

  3. Nagoya University   Institute for Advanced Research   Associate Professor

    2018.4 - 2021.3

  4. Boston University   Department of Biomedical Engineering   Visiting Researcher

    2018.4 - 2019.2

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    Country:United States

  5. Associate Professor, Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya Univ. JAPAN   Graduate School of Engineering Biomolecular Engineering 2   Associate professor

    2017.4

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    Country:Japan

  6. Associate Professor, Department of Biotechnology, Graduate School of Engineering, Nagoya Univ. JAPAN

    2014.6 - 2017.3

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    Country:Japan

  7. Assistant Professor, Graduate School of Engineering Science, Osaka Univ., JAPAN

    2013.4 - 2014.5

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    Country:Japan

  8. Visiting Researcher, R-GIRO, Ritsumeikan Univ., JAPAN

    2009.4 - 2014.3

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    Country:Japan

  9. Project Specific Assistant Professor, Graduate School of Pharmaceutical Sciences, Kyoto Univ., JAPAN

    2009.4 - 2013.3

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    Country:Japan

  10. Visiting Researcher, Toyota Central R&D Labs., INC.

    2007.5 - 2009.3

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    Country:Japan

  11. JSPS Research fellow (PD)

    2007.4

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    Country:Japan

  12. JSPS Research fellow (DC2)

    2006.4 - 2007.3

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    Country:Japan

  13. 21世紀COEプログラム研究員(COE)

    2005.4 - 2006.3

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    Country:Japan

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Education 3

  1. Nagoya University   Graduate School, Division of Engineering   Department of Biotechnology

    - 2007.3

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    Country: Japan

  2. Nagoya University   Graduate School, Division of Engineering

    - 2005.3

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    Country: Japan

  3. Nagoya University   Faculty of Engineering

    1999.4 - 2003.3

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    Country: Japan

Professional Memberships 15

  1. The Society for Biotechnology, Japan

  2. The Society of Chemical Engineers, Japan

  3. Society for Chemistry and Micro-Nano System

  4. 日本筋学会

  5. Japanese Association for Animal Cell Technology (JAACT)

  6. バイオインダストリー協会

  7. 東海化学工業会

  8. 日本筋学会

  9. バイオインダストリー協会

  10. Society for Chemistry and Micro-Nano System

  11. The Society of Chemical Engineers, Japan

  12. The Japan Society of Drug Delivery System

  13. Japanese Association for Animal Cell Technology (JAACT)

  14. The Society for Biotechnology, Japan

  15. 東海化学工業会

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Awards 11

  1. 若手科学者賞(H31年度科学技術分野の文部科学大臣表彰)

    2019   文部科学省  

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    Country:Japan

  2. 第43回生物工学奨励賞(照井賞)・日本生物工学会

    2020.9   日本生物工学会  

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    Award type:International academic award (Japan or overseas)  Country:Japan

  3. 第5回バイオインダストリー奨励賞

    2021.11   バイオインダストリー協会   疾患・創薬研究に資する生体を模倣した新たな神経筋共培養モデルの創製

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    Award type:Award from publisher, newspaper, foundation, etc.  Country:Japan

  4. 化学・生物素材研究開発奨励賞

    2015   一般財団法人バイオインダストリー協会  

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    Country:Japan

  5. 第28回生物工学論文賞・日本生物工学会

    2020.9   日本生物工学会  

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    Award type:Honored in official journal of a scientific society, scientific journal  Country:Japan

  6. 優秀研究賞・化学とマイクロ・ナノシステム学会第40回研究会

    2019   化学とマイクロ・ナノシステム学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  7. 第26回生物工学論文賞・日本生物工学会

    2018   日本生物工学会  

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    Award type:Honored in official journal of a scientific society, scientific journal  Country:Japan

  8. 第51回東海化学工業会賞

    2016   東海化学工業会  

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    Country:Japan

  9. 優秀演題賞・日本動物細胞工学会

    2011   日本動物細胞工学会2011年大会  

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    Country:Japan

  10. 第26回日本DDS学会学術集会優秀発表者賞・日本DDS学会

    2010   日本DDS学会  

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    Country:Japan

  11. 第16回生物工学論文賞・日本生物工学会

    2008   日本生物工学会  

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    Country:Japan

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Papers 127

  1. Separation and enrichment of multiple bile acid micelle-disrupting peptides by adsorption/desorption process with heat-treated porous silica gels

    Iriyama M., Hagawa H., Shimizu S., Akiyama H., Shimizu K., Honda H.

    Biochemical Engineering Journal   Vol. 205   2024.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biochemical Engineering Journal  

    Bile acid (BA) micelle-disrupting peptides are bioactive peptides (BPs) that suppress intestinal cholesterol adsorption and ameliorate blood cholesterol levels. To facilitate their application in the food industry, an effective and straightforward technology for BP separation and enrichment of BPs is required. For this purpose, we assessed the potential of heat-treated (HT) porous silica gels with an enhanced capacity for peptide adsorption/desorption (AD). Given the key characteristics of these peptides involving basic amino acid (AA) residues, we applied casein hydrolysate to HT silica gels for adsorption at neutral pH, where the surface yielded anionic silanolates through deprotonation. Subsequently, desorption was conducted at pH 2, at which point the surface returned to its neutral state. We confirmed a 335-fold increase in the BA micelle-disrupting activity of the resulting hydrolysates. LC-MS/MS analysis identified 783 peptides, confirming that the peptides containing cationic AA residues were selectively enriched, as expected. Moreover, a dose-response of randomly selected 27 peptides with various enrichment levels revealed the presence of multiple active peptides in the enriched groups. These results indicate that our method is effective for the separation and enrichment of BA micelle-disrupting peptides and holds promise for BP production.

    DOI: 10.1016/j.bej.2024.109283

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  2. Electrical pulse stimulation-induced tetanic exercise simulation increases the secretion of extracellular vesicles from C2C12 myotubes

    Murata, A; Akiyama, H; Honda, H; Shimizu, K

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 672   page: 177 - 184   2023.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biochemical and Biophysical Research Communications  

    Extracellular vesicles (EVs) released into the blood during exercise mediate its whole-body health effects. The differentiation of EVs released by skeletal muscle cells in vivo from those released by other cells is challenging, therefore, it is unclear whether exercise increases the number of EVs secreted by skeletal muscle cells. In this study, we investigated whether exercise affects the quantity of EVs released from skeletal muscle cells using in vitro exercise models. C2C12 myotubes were cultured on a gel layer with 1 or 30 Hz electrical pulse stimulation (EPS) to induce contractions as an artificial simulating exercise. We found that tetanic contraction induced by 30 Hz EPS increased the number of secreted EVs. MicroRNA (miRNA)-seq analysis revealed that 30 Hz EPS altered the miRNA in the secreted EVs. Furthermore, expression analysis of genes related to the biogenesis and transport of EVs revealed that the expression of ALG-2 interacting protein X (Alix) was increased in response to 30 Hz EPS, and the peak value of intracellular Ca2+ in myotubes at 30 Hz EPS was higher than that at 1 Hz, indicating that the increase in intracellular Ca2+ concentration may be related to the increased secretion of EVs in response to 30 Hz EPS.

    DOI: 10.1016/j.bbrc.2023.06.054

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  3. l-Anserine Increases Muscle Differentiation and Muscle Contractility in Human Skeletal Muscle Cells

    Nagai, A; Ida, M; Izumo, T; Nakai, M; Honda, H; Shimizu, K

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   Vol. 71 ( 23 ) page: 8952 - 8958   2023.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Agricultural and Food Chemistry  

    l-Anserine, an imidazole peptide, has a variety of physiological activities, but its effects on skeletal muscle differentiation and muscle contractile force remain unknown. Thus, in this study, we investigated the effect of l-anserine on muscle differentiation and muscle contractile force in human skeletal muscle cells. In two-dimensional culture, 1 μM l-anserine significantly increased the myotube diameters (26.5 ± 1.71, 27.7 ± 1.08, and 28.8 ± 0.85 μm with 0, 0.1, and 1 μM l-anserine, respectively) and the expression levels of genes involved in muscle differentiation and the sarcomere structure. In three-dimensional culture, 1 μM l-anserine significantly increased the contractile force of engineered human skeletal muscle tissues cultured on a microdevice (1.99 ± 0.30, 2.17 ± 0.62, 2.66 ± 0.39, and 3.28 ± 0.85 μN with 0, 0.1, 0.5, and 1 μM l-anserine, respectively). l-Anserine also increased the myotube diameters and the proportion of myotubes with sarcomere structures in the cultured tissues. Furthermore, the histamine receptor 1 (H1R) antagonist attenuated the l-anserine-induced increase in the contractile force, suggesting the involvement of H1R in the mechanism of action of l-anserine. This study showed for the first time that l-anserine enhances muscle differentiation and muscle contractility via H1R.

    DOI: 10.1021/acs.jafc.3c01685

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  4. Simple and efficient differentiation of human iPSCs into contractible skeletal muscles for muscular disease modeling

    Rashid, MI; Ito, T; Miya, F; Shimojo, D; Arimoto, K; Onodera, K; Okada, R; Nagashima, T; Yamamoto, K; Khatun, Z; Shimul, RI; Niwa, J; Katsuno, M; Sobue, G; Okano, H; Sakurai, H; Shimizu, K; Doyu, M; Okada, Y

    SCIENTIFIC REPORTS   Vol. 13 ( 1 ) page: 8146   2023.5

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    Pathophysiological analysis and drug discovery targeting human diseases require disease models that suitably recapitulate patient pathology. Disease-specific human induced pluripotent stem cells (hiPSCs) differentiated into affected cell types can potentially recapitulate disease pathology more accurately than existing disease models. Such successful modeling of muscular diseases requires efficient differentiation of hiPSCs into skeletal muscles. hiPSCs transduced with doxycycline-inducible MYOD1 (MYOD1-hiPSCs) have been widely used; however, they require time- and labor-consuming clonal selection, and clonal variations must be overcome. Moreover, their functionality should be carefully examined. Here, we demonstrated that bulk MYOD1-hiPSCs established with puromycin selection rather than G418 selection showed rapid and highly efficient differentiation. Interestingly, bulk MYOD1-hiPSCs exhibited average differentiation properties of clonally established MYOD1-hiPSCs, suggesting that it is possible to minimize clonal variations. Moreover, disease-specific hiPSCs of spinal bulbar muscular atrophy (SBMA) could be efficiently differentiated via this method into skeletal muscle that showed disease phenotypes, suggesting the applicability of this method for disease analysis. Finally, three-dimensional muscle tissues were fabricated from bulk MYOD1-hiPSCs, which exhibited contractile force upon electrical stimulation, indicating their functionality. Thus, our bulk differentiation requires less time and labor than existing methods, efficiently generates contractible skeletal muscles, and may facilitate the generation of muscular disease models.

    DOI: 10.1038/s41598-023-34445-9

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  5. Drug-preloadable methacrylated gelatin microspheres fabricated using an aqueous two-phase system

    Mizukami, Y; Yamaguchi, T; Shiono, M; Takahashi, Y; Shimizu, K; Konishi, S; Takakura, Y; Nishikawa, M

    EUROPEAN POLYMER JOURNAL   Vol. 181   2022.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:European Polymer Journal  

    Gelatin microspheres (GMS) can retain biomolecules and be incorporated into artificial tissues and organs for tissue regeneration. However, the inactivation of biomolecules during the conventional fabrication process of GMS requires postloading of biomolecules to prefabricated GMS. Herein, a novel method for fabricating drug-preloaded GMS using a water-in-water (w/w) emulsification technique, is reported. A highly concentrated gelatin methacrylate (Gm) solution containing fibroblast growth factor 2 (FGF2), a model drug, was emulsified in a highly concentrated polyethylene glycol solution, and the mixture was irradiated with ultraviolet light. The obtained water-in-water gelatin methacrylate microspheres (w/w GmMS) were superior to conventional GMS in terms of stability, FGF2-loading efficiency, and sustained release of FGF2. The FGF2-loaded w/w GmMS efficiently activated the proliferation of adipose tissue-derived mesenchymal stem cells (ASCs). In addition, FGF2-loaded w/w GmMS incorporated into multicellular spheroids of ASCs increased the viability of ASCs in the spheroids. The therapeutic efficacy of ASC spheroids in a wound healing mouse model was significantly improved by the incorporation of FGF2-loaded w/w GmMS. These results indicate that drug-preloadable w/w GmMS can be widely applied in tissue engineering and regenerative medicine strategies.

    DOI: 10.1016/j.eurpolymj.2022.111671

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  6. Quality evaluation of cell spheroids for transplantation by monitoring oxygen consumption using an on-chip electrochemical device.

    Tsujimura M, Kusamori K, Takamura K, Ito T, Kaya T, Shimizu K, Konishi S, Nishikawa M

    Biotechnology reports (Amsterdam, Netherlands)   Vol. 36   page: e00766   2022.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biotechnology Reports  

    Three-dimensional cell spheroids are superior cell-administration form for cell-based therapy which generally exhibit superior functionality and long-term survival after transplantation. Here, we nondestructively measured the oxygen consumption rate of cell spheroids using an on-chip electrochemical device (OECD) and examined whether this rate can be used as a marker to estimate the quality of cell spheroids. Cell spheroids containing NanoLuc luciferase-expressing mouse mesenchymal stem cell line C3H10T1/2 (C3H10T1/2/Nluc) were prepared. Spheroids of high or low quality were prepared by altering the medium change frequency. After transplantation into mice, the high-quality C3H10T1/2/Nluc spheroids exhibited a higher survival rate than the low-quality ones. The oxygen consumption rate of the high-quality C3H10T1/2/Nluc spheroids was maintained at high levels, whereas that of the low-quality spheroids decreased with time. These results indicate that OECD-based measurement of the oxygen consumption rate can be used to estimate the quality of cell spheroids without destructive analysis of the spheroids.

    DOI: 10.1016/j.btre.2022.e00766

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  7. Alignment of Skeletal Muscle Cells Facilitates Acetylcholine Receptor Clustering and Neuromuscular Junction Formation with Co-Cultured Human iPSC-Derived Motor Neurons

    Shimizu, K; Kassai, H; Kamei, Y; Yamamoto, K; Nagashima, T; Maekawa, T; Akiyama, H; Honda, H

    CELLS   Vol. 11 ( 23 )   2022.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cells  

    In vitro neuromuscular junction (NMJ) models are powerful tools for studying neuromuscular disorders. Although linearly patterned culture surfaces have been reported to be useful for the formation of in vitro NMJ models using mouse motor neuron (MNs) and skeletal muscle (SkM) myotubes, it is unclear how the linearly patterned culture surface increases acetylcholine receptor (AChR) clustering, one of the steps in the process of NMJ formation, and whether this increases the in vitro NMJ formation efficiency of co-cultured human MNs and SkM myotubes. In this study, we investigated the effects of a linearly patterned culture surface on AChR clustering in myotubes and examined the possible mechanism of the increase in AChR clustering using gene expression analysis, as well as the effects of the patterned surface on the efficiency of NMJ formation between co-cultured human SkM myotubes and human iPSC-derived MNs. Our results suggest that better differentiation of myotubes on the patterned surface, compared to the flat surface, induced gene expression of integrin α7 and AChR ε-subunit, thereby increasing AChR clustering. Furthermore, we found that the number of NMJs between human SkM cells and MNs increased upon co-culture on the linearly patterned surface, suggesting the usefulness of the patterned surface for creating in vitro human NMJ models.

    DOI: 10.3390/cells11233760

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  8. Analysis of plasmodesmata permeability using cultured tobacco BY-2 cells entrapped in microfluidic chips

    Kurotani, K; Kawakatsu, Y; Kikkawa, M; Tabata, R; Kurihara, D; Honda, H; Shimizu, K; Notaguchi, M

    JOURNAL OF PLANT RESEARCH   Vol. 135 ( 5 ) page: 693 - 701   2022.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Plant Research  

    Plasmodesmata are unique channel structures in plants that link the fluid cytoplasm between adjacent cells. Plants have evolved these microchannels to allow trafficking of nutritious substances as well as regulatory factors for intercellular communication. However, tracking the behavior of plasmodesmata in real time is difficult because they are located inside tissues. Hence, a system was constructed to monitor the movement of substances by plasmodesmata using tobacco BY-2 cells, which are linearly organized cells, and a microfluidic device that traps them in place and facilitates observation. After targeting one cell for photobleaching, recovery of the lost H2B-GFP protein was detected within 200 min. No recovery was detected in that time frame by photobleaching the entire cell filaments. This suggested that the recovery of H2B-GFP protein was not due to de novo protein synthesis, but rather to translocation from neighboring cells. The transport of H2B-GFP protein was not observed when sodium chloride, a compound known to cause plasmodesmata closure, was present in the microfluid channel. Thus, using the microfluidic device and BY-2 cells, it was confirmed that the behavior of plasmodesmata could be observed in real time under controllable conditions.

    DOI: 10.1007/s10265-022-01406-8

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  9. Screening of anti-atrophic peptides by using photo-cleavable peptide array and 96-well scale contractile human skeletal muscle atrophy models

    Yamamoto, K; Ohsumi, S; Nagashima, T; Akiyama, H; Honda, H; Shimizu, K

    BIOTECHNOLOGY AND BIOENGINEERING   Vol. 119 ( 8 ) page: 2196 - 2205   2022.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biotechnology and Bioengineering  

    Skeletal muscle atrophy is characterized by decreases in protein content, myofiber diameter, and contractile force generation. As muscle atrophy worsens the quality of life, the development of anti-atrophic substances is desirable. In this study, we aimed to demonstrate a screening process for anti-atrophic peptides using photo-cleavable peptide array technology and human contractile atrophic muscle models. We developed a 96-well system and established a screening process with less variability. Dexamethasone-induced human atrophic tissue was constructed in the system. Eight peptides were selected from the literature and used for the screening of peptides for preventing the decrease of the contractile forces of tissues. The peptide QIGFIW, which showed preventive activity, was selected as the seed sequence. As a result of amino acid substitution, we obtained QIGFIQ as a peptide with higher anti-atrophic activity. These results indicate that the combinatorial use of the photo-cleavable peptide array technology and 96-well screening system could comprise a powerful approach to obtaining anti-atrophic peptides, and suggest that the 96-well screening system and atrophic model represent a practical and powerful tool for the development of drugs/functional food ingredients.

    DOI: 10.1002/bit.28125

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  10. Mechanical Regulation Of Provisional Matrix Assembly In 3D Fibrous Microtissues International coauthorship

    Eyckmans, J; Das, S; Shimizu, K; Chen, C

    WOUND REPAIR AND REGENERATION   Vol. 30 ( 2 ) page: A20 - A21   2022.3

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  11. Selective concentration of antimicrobial peptides to heat-treated porous silica gel using adsorption/desorption

    Hagawa, H; Imai, K; Gao, ZW; Taniguchi, M; Shimizu, K; Honda, H

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   Vol. 133 ( 2 ) page: 161 - 167   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Bioscience and Bioengineering  

    Heat-treated porous silica gel (HT silica gel) previously developed by our group has selectively adsorbed cationic peptides at a pH of 7. Therefore, we focused on the use of antimicrobial peptides (AMPs) as bioactive peptides (BPs). First, 32 AMPs and 32 randomly designed peptides were generated using Fmoc solid synthesis, and their adsorption ratio to HT-silica gel was investigated. Thirty two AMPs showed a relatively higher adsorption ratio of 58.8% compared to that of randomly designed peptides, which was 35.3%. Desorption conditions were investigated using Amyl-1-18 antimicrobial peptides. Next, pepsin hydrolysate from rice endosperm protein (REP) powder was prepared by ourselves. The REP hydrolysate containing dry matter (7.5 mg) was applied to the adsorption/desorption (AD) procedure using HT silica gel to obtain 1.6 mg of AD hydrolysate. When the two hydrolysates were subjected to mass spectrometry, 305 concentrated peptides were obtained. In total, 26 peptides with high content and high enrichment ratios were listed and synthesized. When the antimicrobial activity of these 26 peptides was evaluated using Cutibacterium acnes, five peptides consisting of 12–27 amino acids were identified as novel AMPs. Two of these peptides, which were derived from rice glutelin, showed antimicrobial activity against all four microbes, including Porphyromonas gingivalis, Escherichia coli, and Streptococcus mutans. In the present study, we showed that AMPs could be easily enriched from protein hydrolysate using HT silica gel. The adsorption/desorption procedure using HT silica gel was confirmed to be a useful tool for convenient BP separation.

    DOI: 10.1016/j.jbiosc.2021.11.002

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  12. Intravenous injection of mesenchymal stem cell spheroids improves the pulmonary delivery and prolongs in vivo survival

    Shimazawa, Y; Kusamori, K; Tsujimura, M; Shimomura, A; Takasaki, R; Takayama, Y; Shimizu, K; Konishi, S; Nishikawa, M

    BIOTECHNOLOGY JOURNAL   Vol. 17 ( 1 ) page: e2100137   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biotechnology Journal  

    Background: Because of the excellent therapeutic potential, mesenchymal stem cells (MSCs) have been used as cell therapeutics for various diseases. However, the survival rate and duration of MSCs after transplantation are extremely low and short, respectively. To solve these problems, in this study, we prepared multicellular spheroids of MSCs and investigated their survival and function after intravenous injection in mice. Methods and Results: The murine adipose-derived MSC line m17.ASC was cultured in agarose-based microwell plates to obtain size-controlled m17.ASC spheroids of an average diameter and cell number of approximately 170 μm and 1100 cells/spheroid, respectively. The intravenously injected m17.ASC spheroids mainly accumulated in the lung and showed a higher survival rate than suspended m17.ASC cells during the experimental period of 7 days. m17.ASC spheroids efficiently reduced the lipopolysaccharide-induced increase in plasma concentrations of interleukin-6 and tumor necrosis factor-α. Conclusions: These results indicate that spheroid formation improved the pulmonary delivery and survival of MSCs, as well as their therapeutic potential against inflammatory pulmonary diseases.

    DOI: 10.1002/biot.202100137

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  13. Development of microfluidic chip for entrapping tobacco BY-2 cells

    Shimizu, K; Kawakatsu, Y; Kurotani, KI; Kikkawa, M; Tabata, R; Kurihara, D; Honda, H; Notaguchi, M

    PLOS ONE   Vol. 17 ( 4 ) page: e0266982   2022

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PLoS ONE  

    The tobacco BY-2 cell line has been used widely as a model system in plant cell biology. BY-2 cells are nearly transparent, which facilitates cell imaging using fluorescent markers. As cultured cells are drifted in the medium, therefore, it was difficult to observe them for a long period. Hence, we developed a microfluidic device that traps BY-2 cells and fixes their positions to allow monitoring the physiological activity of cells. The device contains 112 trap zones, with parallel slots connected in series at three levels in the flow channel. BY-2 cells were cultured for 7 days and filtered using a sieve and a cell strainer before use to isolate short cell filaments consisting of only a few cells. The isolated cells were introduced into the flow channel, resulting in entrapment of cell filaments at 25 out of 112 trap zones (22.3%). The cell numbers increased through cell division from 1 to 4 days after trapping with a peak of mitotic index on day 2. Recovery experiments of fluorescent proteins after photobleaching confirmed cell survival and permeability of plasmodesmata. Thus, this microfluidic device and one-dimensional plant cell samples allowed us to observe cell activity in real time under controllable conditions.

    DOI: 10.1371/journal.pone.0266982

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  14. Detection of protease digestion site using fluorescence labeled peptide array and construction of machine-learning prediction model

    Mizutani R., Mori Y., Ogawa S., Tazoe K., Akiyama H., Shimizu K., Honda H.

    Seibutsu-kogaku Kaishi   Vol. 100 ( 10 ) page: 528 - 540   2022

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Seibutsu-kogaku Kaishi  

    For the prediction of protease digestion site, 1990 kinds of tetramer peptide were designed as a library, of which N terminal end was fluorescence labelled. Decrease of fluorescence intensity of each peptide was quantitatively determined and used as a training data for Random Forest (RF) modeling. All of dipeptides bond as a protease substrate were included in 1990 tetramer peptides. As an explanatory variable for model construction, 532 parameters were prepared and those were included not only appearance of amino acid residue or dipeptides but also positioning parameters (PP) or global parameters (GP) to explain the peptide property. Trypsin for biochemistry grade was used for hydrolysis. After digesting at pH 8, the histogram of digestion ratio was appeared that tetramers with arginine residue (R) and lysine residue (K) could be expectedly digested at higher ratio compared with tetramers without R or K. Constructed pH 8-RF model showed 77 % of prediction accuracy. The explanatory parameters with top 10 higher importance in pH 8-RF model were both of appearance of K and 9 GPs. GPs were including 4 isoelectric parameters and 1 polarity parameter, of which K or R residue have relatively large value. Digestion site of α-lactalbumin was determined using pH 8-RF model and the protein was actually digested by trypsin. When the hydrolysate was analyzed by LC-MS/MS, 42 peptides were identified. Fourteen sites among 19 predicted digestion sites were coincided with each other. Many peptide fragments digested at 69Y-70G site or 50F-51H site was detected and it was strongly suggested to be digested by chymotrypsin as a contaminated protease. These sites were fairly predicted by constructed RF model. In addition, trypsin digestion at pH 5 was carried out to investigate the effect of pH decrease on trypsin digestion. The prediction accuracy of pH 5-RF model was only 59 %. The parameters with top 10 higher importance in pH 5-RF model were including 4 GPs which was the same with 4 isoelectric parameter in pH 8 model. Twenty digestion sites of α-lactalbumin were predicted from pH 5-RF model. α-lactalbumin was digested at pH 5 by trypsin, and 64 peptides were identified. The predicted sites were compared with identified fragments at the region from 48T to 77K in which a lot of fragments were detected. It was concluded that constructed model could fairly predict some of newly identified sites and could roughly grasp slight modification of digestion site by pH change. The proposed methodology, which contained 1990 kinds of tetramer peptides as a library, 532 explanatory parameters and RF model, was effective for prediction of protease digestion site.

    DOI: 10.34565/seibutsukogaku.100.10_528

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  15. Agonist/Antagonist Activity of Oxytocin Variants Obtained from Free Cyclic Peptide Libraries Generated via Amino Acid Substitution

    Kinoshita, R; Kozaki, I; Shimizu, K; Shibata, T; Ochiai, A; Honda, H

    ACS OMEGA   Vol. 6 ( 46 ) page: 31244 - 31252   2021.11

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    We established a method for synthesizing a free cyclic peptide library via peptide array synthesis to demonstrate the sequence activity of cyclic peptides. Variants of the cyclic nonapeptide oxytocin (OXT) were synthesized via residue substitution. Natural amino acids (AAs) were classified into eight groups based on their physical properties and the size of their side chains, and a representative AA from each group was selected for residue substitution. All OXT variants were systematically evaluated for agonist/antagonist activity. Consequently, no improvement in agonist activity was observed, although substitution of the P4 and P8 residues resulted in decreased activity due to AA substitution. A few OXT variants exhibited antagonistic activity. In particular, the variants with P2 Leu residue substitution (Y2L) and Phe substitutions at residues 4 (Q4F), 5 (N5F), and 7 (P7F) showed high antagonistic activity. Variant Y2W was found to have the highest inhibitory effect, with a dissociation constant of 44 nM, which was comparable to that of the commercial antagonist atosiban (21 nM). Therefore, a free cyclic peptide library constructed via substitution with a natural AA residue was confirmed to be a powerful tool for bioactive peptide screening.

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  16. Calcium Peroxide-Containing Polydimethylsiloxane-Based Microwells for Inhibiting Cell Death in Spheroids through Improved Oxygen Supply

    Yuya Mizukami, Yuki Takahashi, Kazunori Shimizu, Satoshi Konishi, Yoshinobu Takakura, Makiya Nishikawa

    Biological and Pharmaceutical Bulletin   Vol. 44 ( 10 ) page: 1458 - 1464   2021.10

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    DOI: 10.1248/bpb.b21-00269

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  17. Microarray profiling of gene expression in C2C12 myotubes trained by electric pulse stimulation.

    Hideaki Fujita, Masanobu Horie, Kazunori Shimizu, Eiji Nagamori

    Journal of bioscience and bioengineering   Vol. 132 ( 4 ) page: 417 - 422   2021.10

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    Electric pulse-stimulated C2C12 myotubes are gaining interest in the field of muscle physiology and biotechnology because electric pulse stimulation (EPS) enhances sarcomere structure development and active tension generation capability. Recently, we found that termination of EPS results in the rapid loss of active tension generation accompanied by disassembly of the sarcomere structure, which may represent an in vitro muscle atrophy model. To elucidate the molecular mechanism underlying this rapid loss of active tension generation and sarcomere structure disassembly after termination of EPS, we performed transcriptomic analysis using microarray. After termination of EPS, 74 genes were upregulated and 120 genes were downregulated after 30 min; however, atrophy-related genes were not found among these genes. To further assess the effect of EPS on gene expression, we re-applied EPS after its termination for 8 h and searched for genes whose expression was reversed. Four genes were upregulated by termination of EPS and downregulated by the re-application of EPS, whereas two genes were downregulated by termination of EPS and upregulated by the re-application of EPS. Although none of these genes were atrophy- or hypertrophy-related, the results presented in this study will contribute to the understanding of gene expression changes that mediate rapid loss of active tension generation and sarcomere structure disassembly following termination of EPS in C2C12 myotubes.

    DOI: 10.1016/j.jbiosc.2021.06.016

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  18. In Silico Screening of a Bile Acid Micelle Disruption Peptide for Oral Consumptions from Edible Peptide Database

    Imai, K; Takeuchi, Y; Shimizu, K; Honda, H

    FOODS   Vol. 10 ( 10 )   2021.10

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    Recently, many bioactive peptides have been identified using bioinformatics tools. Previously, our group developed a method to screen dual-functional peptides that have direct intestinal delivery with porous silica gel and bile acid micelle disruption. However, newly designed peptides were not found in any storage protein. Therefore, in this study, in silico screening was performed using a 350,000 edible peptide library consisting of 4-to 7-mer independent peptides. As an initial screening, all edible peptides were applied to the random forest model to select predicted positive peptides. For a second screening, the peptides were assessed for the possibility of intestinal delivery using a 3D color map. From this approach, three novel dual-functional peptides, VYVFDE, WEFIDF, and VEEFYC were identified, and all of them were derived from storage proteins (legumin, myosin, and 11S globulin). In particular, VEEFYCS, in which a serine residue (S) is added to VEEFYC, was assumed to be released by thermolysin from the 11S-globulin derived from Ginkgo biloba by LC-MS/MS analysis. VEEFYCS was found to have suitable direct intestinal delivery and bile acid micelle disruption activity.

    DOI: 10.3390/foods10102496

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  19. Simple stain-free screening method for pectinolytic microorganisms under alkalophilic conditions

    Ishihara, M; Kikkawa, M; Shimizu, K; Suzuki, H; Honda, H

    BIOTECHNOLOGY LETTERS   Vol. 43 ( 9 ) page: 1905 - 1911   2021.9

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    Objectives: To develop a simple pectin-degrading microorganism screening method. Results: We developed a method utilizing the phenomenon whereby cooling an alkaline agar medium containing pectin causes the agar to become cloudy. This highly simplified method involves culturing the microorganisms on pectin-containing agar medium until colony formation is observed, and subsequent overnight cooling of the agar medium to 4 °C. Using this simple procedure, we successfully identified pectin-degrading microorganisms by observing colonies with halos on the clouded agar medium. We used alkaline pectinase and Bacillus halodurans, which is known to secrete alkaline pectinase, to establish the screening method. We demonstrated the screening of pectin-degrading microorganisms using the developed method and successfully isolated pectin-degrading microorganisms (Paenibacillus sp., Bacillus clausii, and Bacillus halodurans) from a soil sample. Conclusions: The developed method is useful for identifying pectin-degrading microorganisms.

    DOI: 10.1007/s10529-021-03162-6

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  20. Machine learning screening of bile acid-binding peptides in a peptide database derived from food proteins

    Imai, K; Shimizu, K; Honda, H

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 16123   2021.8

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    Bioactive peptides (BPs) are protein fragments that exhibit a wide variety of physicochemical properties, such as basic, acidic, hydrophobic, and hydrophilic properties; thus, they have the potential to interact with a variety of biomolecules, whereas neither carbohydrates nor fatty acids have such diverse properties. Therefore, BP is considered to be a new generation of biologically active regulators. Recently, some BPs that have shown positive benefits in humans have been screened from edible proteins. In the present study, a new BP screening method was developed using BIOPEP-UWM and machine learning. Training data were initially obtained using high-throughput techniques, and positive and negative datasets were generated. The predictive model was generated by calculating the explanatory variables of the peptides. To understand both site-specific and global characteristics, amino acid features (for site-specific characteristics) and peptide global features (for global characteristics) were generated. The constructed models were applied to the peptide database generated using BIOPEP-UWM, and bioactivity was predicted to explore candidate bile acid-binding peptides. Using this strategy, seven novel bile acid-binding peptides (VFWM, QRIFW, RVWVQ, LIRYTK, NGDEPL, PTFTRKL, and KISQRYQ) were identified. Our novel screening method can be easily applied to industrial applications using whole edible proteins. The proposed approach would be useful for identifying bile acid-binding peptides, as well as other BPs, as long as a large amount of training data can be obtained.

    DOI: 10.1038/s41598-021-95461-1

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  21. Development of a human neuromuscular tissue-on-a-chip model on a 24-well-plate-format compartmentalized microfluidic device. International journal

    Kazuki Yamamoto, Nao Yamaoka, Yu Imaizumi, Takunori Nagashima, Taiki Furutani, Takuji Ito, Yohei Okada, Hiroyuki Honda, Kazunori Shimizu

    Lab on a chip   Vol. 21 ( 10 ) page: 1897 - 1907   2021.5

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    Engineered three-dimensional models of neuromuscular tissues are promising for use in mimicking their disorder states in vitro. Although several models have been developed, it is still challenging to mimic the physically separated structures of motor neurons (MNs) and skeletal muscle (SkM) fibers in the motor units in vivo. In this study, we aimed to develop microdevices for precisely compartmentalized coculturing of MNs and engineered SkM tissues. The developed microdevices, which fit a well of 24 well plates, had a chamber for MNs and chamber for SkM tissues. The two chambers were connected by microtunnels for axons, permissive to axons but not to cell bodies. Human iPSC (hiPSC)-derived MN spheroids in one chamber elongated their axons into microtunnels, which reached the tissue-engineered human SkM in the SkM chamber, and formed functional neuromuscular junctions with the muscle fibers. The cocultured SkM tissues with MNs on the device contracted spontaneously in response to spontaneous firing of MNs. The addition of a neurotransmitter, glutamate, into the MN chamber induced contraction of the cocultured SkM tissues. Selective addition of tetrodotoxin or vecuronium bromide into either chamber induced SkM tissue relaxation, which could be explained by the inhibitory mechanisms. We also demonstrated the application of chemical or mechanical stimuli to the middle of the axons of cocultured tissues on the device. Thus, compartmentalized neuromuscular tissue models fabricated on the device could be used for phenotypic screening to evaluate the cellular type specific efficacy of drug candidates and would be a useful tool in fundamental research and drug development for neuromuscular disorders.

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  22. Electrospray propelled by ionic wind in a bipolar system for direct delivery of charge reduced nanoparticles International coauthorship

    Dau, VT; Vu, TH; Tran, CD; Nguyen, TV; Nguyen, TK; Dinh, T; Phan, HP; Shimizu, K; Nguyen, NT; Dao, DV

    APPLIED PHYSICS EXPRESS   Vol. 14 ( 5 )   2021.5

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    We present a conceptual design to generate and deliver nanoparticles in one unique system based on electrohydrodynamic atomisation (EHDA) without the restriction of the collector. The present EHDA bipolar configuration consists of a capillary nozzle and a pin, both act as emitters and as the reference electrodes of each other. Under an applied voltage, the capillary nozzle sprays droplets while the pin generates ion wind via corona discharge. During spraying process, droplets' charge is significantly reduced by interacting with counter ions and propelled away from the electrodes by the momentum of ion winds accumulated from corona discharge. Thus, the present technique can yield promising applications in effective respiratory delivery of nanomedicine. © 2021 The Japan Society of Applied Physics.

    DOI: 10.35848/1882-0786/abf36b

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  23. Screening of a novel free fatty acid receptor 1 (FFAR1) agonist peptide by phage display and machine learning based-amino acid substitution Reviewed

    Yoshioka K.

    Biochemical and Biophysical Research Communications   Vol. 550   page: 177 - 183   2021.4

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    DOI: 10.1016/j.bbrc.2021.02.142

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  24. Increasing the activity of cell adherent cyclic NGR peptides by optimizing the peptide length and amino acid character Reviewed

    Kozaki I.

    Journal of Peptide Science   Vol. 27 ( 1 )   2021.1

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    DOI: 10.1002/psc.3287

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  25. Screening of FFAR1-Activating Peptides by Molecular Structural Analysis

    Yoshioka, K; Yamashita, H; Fujitani, M; Kato, R; Shimizu, K; Honda, H

    KAGAKU KOGAKU RONBUNSHU   Vol. 47 ( 3 ) page: 64 - 68   2021

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    To find FFAR1-activating peptides consisting of natural amino acid residues, molecular structure analysis was performed by hierarchical clustering using extraction of physicochemical parameters. When 3 mer to 6 mer peptide libraries were prepared and the molecular structure of each was compared with 5 chemical agonists, 12 peptides with high correlation coefficients of physicochemical parameters were found from the 6 mer peptide library. these peptides were then synthesized by Fmoc solid phase synthesis, and their activity was assessed by TGFα shedding assay using FFAR1-expressing HEK293. As a result, two peptides, GCGGSS and GASGCC, were identified as peptide agonists with relatively high activity. Although these peptides showed approximately one fithh of the activity of chemical agonist GW9508, they are the first examples that we know of FFAR1-activating peptides consisting of natural amino acid residues.

    DOI: 10.1252/kakoronbunshu.47.64

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  26. Study on functional expression and evaluation of cultured skeletal muscle cells using microfabricated devices

    Shimizu K

    Seibutsu-kogaku Kaishi   Vol. 99 ( 3 ) page: 122 - 128   2021

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    DOI: 10.34565/seibutsukogaku.99.3_122

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  27. Machine Learning-Based Amino Acid Substitution of Short Peptides: Acquisition of Peptides with Enhanced Inhibitory Activities against α-Amylase and α-Glucosidase

    Yamashita H.

    ACS Biomaterials Science and Engineering   Vol. 6 ( 11 ) page: 6117 - 6125   2020.11

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    DOI: 10.1021/acsbiomaterials.0c01010

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  28. Bile acid micelle disruption activity of short-chain peptides from tryptic hydrolyzate of edible proteins

    Ito M.

    Journal of Bioscience and Bioengineering   Vol. 130 ( 5 ) page: 514 - 519   2020.11

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    DOI: 10.1016/j.jbiosc.2020.07.006

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  29. In Vitro Model of Human Skeletal Muscle Tissues with Contractility Fabricated by Immortalized Human Myogenic Cells

    Nagashima T.

    Advanced Biosystems   Vol. 4 ( 11 )   2020.11

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    DOI: 10.1002/adbi.202000121

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  30. Effect of cell-extracellular matrix interaction on myogenic characteristics and artificial skeletal muscle tissue.

    Ding R, Horie M, Nagasaka S, Ohsumi S, Shimizu K, Honda H, Nagamori E, Fujita H, Kawamoto T

    Journal of bioscience and bioengineering   Vol. 130 ( 1 ) page: 98-105 - 105   2020.7

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    DOI: 10.1016/j.jbiosc.2020.02.008

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  31. Efficient capturing of circulating tumor cells using a magnetic capture column and a size-selective filter

    Yamamoto S

    Bioprocess and Biosystems Engineering   Vol. 38 ( 9 )   2020.5

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    DOI: 10.1007/s00449-015-1412-9

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  32. Fabrication of contractile skeletal muscle tissues using directly converted myoblasts from human fibroblasts.

    Shimizu K, Ohsumi S, Kishida T, Mazda O, Honda H

    Journal of bioscience and bioengineering   Vol. 129 ( 5 ) page: 632-637 - 637   2020.5

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    DOI: 10.1016/j.jbiosc.2019.11.013

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  33. Disulfide linked hetero dimeric peptide arrays for screening functional peptides inside cells.

    Kozaki I, Shimizu K, Honda H

    Journal of bioscience and bioengineering   Vol. 129 ( 5 ) page: 613-618 - 618   2020.5

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    DOI: 10.1016/j.jbiosc.2019.11.012

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  34. Tissue suction-mediated gene transfer to the beating heart in mice

    Taniguchi Yota, Oyama Natsuko, Fumoto Shintaro, Kinoshita Hideyuki, Yamashita Fumiyoshi, Shimizu Kazunori, Hashida Mitsuru, Kawakami Shigeru

    PLOS ONE   Vol. 15 ( 2 ) page: e0228203   2020.2

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    DOI: 10.1371/journal.pone.0228203

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  35. Miniaturized skeletal muscle tissue fabrication for measuring contractile activity

    Yoshioka K.

    Journal of Bioscience and Bioengineering     2020

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    DOI: 10.1016/j.jbiosc.2020.11.014

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  36. Incorporation of gelatin microspheres into hepg2 human hepatocyte spheroids for functional improvement through improved oxygen supply to spheroid core

    Mizukami Y.

    Biological and Pharmaceutical Bulletin   Vol. 43 ( 8 ) page: 1220 - 1225   2020

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    DOI: 10.1248/BPB.B20-00141

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  37. Open-Chamber Co-Culture Microdevices for Single-Cell Analysis of Skeletal Muscle Myotubes and Motor Neurons with Neuromuscular Junctions

    Yamaoka Nao, Shimizu Kazunori, Imaizumi Yu, Ito Takuji, Okada Yohei, Honda Hiroyuki

    BIOCHIP JOURNAL   Vol. 13 ( 2 ) page: 127-132   2019.6

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    DOI: 10.1007/s13206-018-3202-3

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  38. Regulation of the Distribution of Cells in Mixed Spheroids by Altering Migration Direction

    Mizukami Yuya, Takahashi Yuki, Shimizu Kazunori, Konishi Satoshi, Takakura Yoshinobu, Nishikawa Maikiya

    TISSUE ENGINEERING PART A   Vol. 25 ( 5-6 ) page: 390-398   2019.3

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    DOI: 10.1089/ten.tea.2018.0063

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  39. Searching for high-binding peptides to bile acid for inhibition of intestinal cholesterol absorption using principal component analysis.

    Ito M, Shimizu K, Honda H

    Journal of bioscience and bioengineering   Vol. 127 ( 3 ) page: 366-371   2019.3

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    DOI: 10.1016/j.jbiosc.2018.08.006

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  40. Regulation of the Distribution of Cells in Mixed Spheroids by Altering Migration Direction.

    Mizukami Y, Takahashi Y, Shimizu K, Konishi S, Takakura Y, Nishikawa M

    Tissue engineering. Part A   Vol. 25 ( 5-6 ) page: 390-398   2019.3

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    DOI: 10.1089/ten.TEA.2018.0063

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  41. Searching for high-binding peptides to bile acid for inhibition of intestinal cholesterol absorption using principal component analysis

    Ito Masako, Shimizu Kazunori, Honda Hiroyuki

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   Vol. 127 ( 3 ) page: 366-371   2019.3

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    DOI: 10.1016/j.piosc.2018.08.006

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  42. Selective Elimination of Bitter Peptides by Adsorption to Heat-treated Porous Silica Gel Reviewed

    Imai, K, Ikeda, A, Shimizu, K, Honda, H

    Food Science and Technology Research   Vol. 25 ( 2 ) page: 179-186 - 186   2019

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    DOI: 10.3136/fstr.25.179

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  43. Pep-MS assay: Protease hydrolysis assay system using photo-cleavable peptide array and mass spectrometer Reviewed

    Kurimoto, M, Shimizu, K, Ochi, H, Abe, F, Honda, H

    Journal of Bioscience and Bioengineering   Vol. 128 ( 2 ) page: 156-161 - 161   2019

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    DOI: 10.1016/j.jbiosc.2019.02.005

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  44. Predictive selection and evaluation of appropriate functional peptides for intestinal delivery with a porous silica gel Reviewed

    Imai, K, Shimizu, K, Honda, H

    Journal of Bioscience and Bioengineering   Vol. 128 ( 1 ) page: 44-49 - 49   2019

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    DOI: 10.1016/j.jbiosc.2019.01.001

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  45. Selective Elimination of Bitter Peptides by Adsorption to Heat-treated Porous Silica Gel Reviewed

    Imai, K., Ikeda, A., Shimizu, K., Honda, H.

    Food Science and Technology Research   Vol. 25 ( 2 ) page: 179-186   2019

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  46. Pep-MS assay: Protease hydrolysis assay system using photo-cleavable peptide array and mass spectrometer Reviewed

    Kurimoto, M., Shimizu, K., Ochi, H., Abe, F., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 128 ( 2 ) page: 156-161   2019

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  47. Predictive selection and evaluation of appropriate functional peptides for intestinal delivery with a porous silica gel Reviewed

    Imai, K., Shimizu, K., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 128 ( 1 ) page: 44-49   2019

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  48. In-process evaluation of culture errors using morphology-based image analysis

    Imai Yuta, Yoshida Kei, Matsumoto Megumi, Okada Mai, Kanie Kei, Shimizu Kazunori, Honda Hiroyuki, Kato Ryuji

    REGENERATIVE THERAPY   Vol. 9   page: 15-23   2018.12

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    DOI: 10.1016/j.reth.2018.06.001

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  49. Selective Elimination of Human Induced Pluripotent Stem Cells Using Medium with High Concentration of L-Alanine

    Nagashima Takunori, Shimizu Kazunori, Matsumoto Ryo, Honda Hiroyuki

    SCIENTIFIC REPORTS   Vol. 8   2018.8

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    DOI: 10.1038/s41598-018-30936-2

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  50. Interaction between porous silica gel microcarriers and peptides for oral administration of functional peptides

    Imai Kento, Shimizu Kazunori, Kamimura Mitsuhiro, Honda Hiroyuki

    SCIENTIFIC REPORTS   Vol. 8   2018.7

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    DOI: 10.1038/s41598-018-29345-2

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  51. Determining Transgene Expression Characteristics Using a Suction Device with Multiple Hole Adjusting a Left Lateral Lobe of the Mouse Liver

    Haraguchi Ayana, Fuchigami Yuki, Kawaguchi Maho, Fumoto Shintaro, Ohyama Kaname, Shimizu Kazunori, Hagimori Masayori, Kawakami Shigeru

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   Vol. 41 ( 6 ) page: 944-950   2018.6

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  52. Determining Transgene Expression Characteristics Using a Suction Device with Multiple Hole Adjusting a Left Lateral Lobe of the Mouse Liver

    Haraguchi Ayana, Fuchigami Yuki, Kawaguchi Maho, Fumoto Shintaro, Ohyama Kaname, Shimizu Kazunori, Hagimori Masayori, Kawakami Shigeru

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   Vol. 41 ( 6 ) page: 944-950   2018.6

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  53. Mutations responsible for alcohol tolerance in the mutant of Synechococcus elongatus PCC 7942 (SY1043) obtained by single-cell screening system

    Hirokawa Yasutaka, Kanesaki Yu, Arai Sayuri, Saruta Fumiko, Hayashihara Kayoko, Murakami Akio, Shimizu Kazunori, Honda Hiroyuki, Yoshikawa Hirofumi, Hanai Taizo

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   Vol. 125 ( 5 ) page: 572-577   2018.5

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    DOI: 10.1016/j.jbiosc.2017.11.012

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  54. Control of polarization and tumoricidal activity of macrophages by multicellular spheroid formation

    Tanaka Yutaro, Nishikawa Makiya, Mizukami Yuya, Kusamori Kosuke, Ogino Yuka, Nishimura Shunsuke, Shimizu Kazunori, Konishi Satoshi, Takahashi Yuki, Takakura Yoshinobu

    JOURNAL OF CONTROLLED RELEASE   Vol. 270   page: 177-183   2018.1

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    DOI: 10.1016/j.jconrel.2017.12.006

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  55. Determining Transgene Expression Characteristics Using a Suction Device with Multiple Hole Adjusting a Left Lateral Lobe of the Mouse Liver.

    Haraguchi A, Fuchigami Y, Kawaguchi M, Fumoto S, Ohyama K, Shimizu K, Hagimori M, Kawakami S

    Biological & pharmaceutical bulletin   Vol. 41 ( 6 ) page: 944 - 950   2018

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    DOI: 10.1248/bpb.b18-00094

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  56. Characterization of transgene expression and pDNA distribution of the suctioned kidney in mice.

    Oyama N, Fuchigami Y, Fumoto S, Sato M, Hagimori M, Shimizu K, Kawakami S

    Drug delivery   Vol. 24 ( 1 ) page: 906-917   2017.11

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    DOI: 10.1080/10717544.2017.1333171

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  57. Morphology-based non-invasive quantitative prediction of the differentiation status of neural stem cells.

    Fujitani M, Huddin NS, Kawai S, Kanie K, Kiyota Y, Shimizu K, Honda H, Kato R

    Journal of bioscience and bioengineering   Vol. 124 ( 3 ) page: 351-358   2017.9

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    DOI: 10.1016/j.jbiosc.2017.04.006

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  58. Using size-controlled multicellular spheroids of murine adenocarcinoma cells to efficiently establish pulmonary tumors in mice.

    Nishikawa T, Tanaka Y, Kusamori K, Mizuno N, Mizukami Y, Ogino Y, Shimizu K, Konishi S, Takahashi Y, Takakura Y, Nishikawa M

    Biotechnology journal   Vol. 12 ( 8 )   2017.8

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    DOI: 10.1002/biot.201600513

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  59. Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system.

    Kozaki I, Shimizu K, Honda H

    Journal of bioscience and bioengineering   Vol. 124 ( 2 ) page: 209-214   2017.8

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    DOI: 10.1016/j.jbiosc.2017.03.013

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  60. Alcohol-tolerant mutants of cyanobacterium Synechococcus elongatus PCC 7942 obtained by single-cell mutant screening system

    Arai Sayuri, Hayashihara Kayoko, Kanamoto Yuki, Shimizu Kazunori, Hirokawa Yasutaka, Hanai Taizo, Murakami Akio, Honda Hiroyuki

    BIOTECHNOLOGY AND BIOENGINEERING   Vol. 114 ( 8 ) page: 1771-1778   2017.8

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    DOI: 10.1002/bit.26307

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  61. Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

    Shimizu K, Genma R, Gotou Y, Nagasaka S, Honda H

    Bioengineering (Basel, Switzerland)   Vol. 4 ( 2 ) page: 56   2017.6

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    DOI: 10.3390/bioengineering4020056

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    PubMed

  62. Image-based cell quality evaluation to detect irregularities under same culture process of human induced pluripotent stem cells.

    Nagasaka R, Gotou Y, Yoshida K, Kanie K, Shimizu K, Honda H, Kato R

    Journal of bioscience and bioengineering   Vol. 123 ( 5 ) page: 642-650   2017.5

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    DOI: 10.1016/j.jbiosc.2016.12.015

    Scopus

    PubMed

  63. Optimization of Albumin Secretion and Metabolic Activity of Cytochrome P450 1A1 of Human Hepatoblastoma HepG2 Cells in Multicellular Spheroids by Controlling Spheroid Size.

    Nishikawa T, Tanaka Y, Nishikawa M, Ogino Y, Kusamori K, Mizuno N, Mizukami Y, Shimizu K, Konishi S, Takahashi Y, Takakura Y

    Biological & pharmaceutical bulletin   Vol. 40 ( 3 ) page: 334 - 338   2017

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    DOI: 10.1248/bpb.b16-00833

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    PubMed

  64. Exploring high-affinity binding properties of octamer peptides by principal component analysis of tetramer peptides Reviewed

    Kume, A., Kawai, S., Kato, R., Iwata, S., Shimizu, K., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 123 ( 2 ) page: 230-238   2017

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  65. Ex vivo culture of circulating tumor cells using magnetic force-based cell co-culture on a fibroblast feeder layer Reviewed

    Yamamoto, S., Shimizu, K., Fei, J., Iwata, H., Okochi, M., Nakanishi, H., Honda, H.

    Biotechnology Journal     page: in press   2017

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  66. Three-dimensional cultured skeletal muscle tissue atrophy model induced with dexamethasone Reviewed

    Shimizu, K., Genma, R., Goto, Y., Nagasaka, S., Honda, H.

    Bioengineering   Vol. 4 ( 2 ) page: 56   2017

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  67. Morphology-based non-invasive quantitative prediction of the differentiation status of neural stem cells Reviewed

    Fujitani, M., Huddin, N.S., Kawai, S., Kanie, K., Kiyota, Y., Shimizu, K., Honda, H., Kato, R.

    Journal of Bioscience and Bioengineering     page: in press   2017

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  68. Characterization of transgene expression and pDNA distribution in the kidney by renal suction-mediated transfection method in mice Reviewed

    Oyama, N., Fuchigami, Y., Fumoto, S., Sato, M., Hagimori M., Shimizu, K., Kawakami, S.

    Drug Delivery   Vol. 24 ( 1 ) page: 906-917   2017

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  69. Using size-controlled multicellular spheroids of murine adenocarcinoma cells to efficiently establish pulmonary tumors in mice Reviewed

    Nishikawa, T., Tanaka, Y., Nishikawa, M., Kusamori, K., Mizuno, N., Mizukami, Y., Ogino, Y., Shimizu, K., Konishi, S., Takahashi, Y., Yoshinobu Takakura

    Biotechnology Journal     page: in press   2017

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  70. Alcohol-tolerant mutants of cyanobacterium Synechococcus elongatus PCC7942 obtained by UV-C induced random mutagenesis and single cell screening system Reviewed

    Arai, S*., Hayashihara, K*., Kanamoto, Y., Shimizu, K., Hirokawa, Y., Hanai, T., Murakami, A., Honda, H.

    Biotechnology and Bioengineering   Vol. 114 ( 8 ) page: 1771-1778   2017

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  71. Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system Reviewed

    Kozaki, I., Shimizu, K., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 124 ( 2 ) page: 209-214   2017

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  72. Image-based cell quality evaluation to detect irregularities under same culture process of human induced pluripotent stem cells Reviewed

    Nagasaka, R., Gotou, Y., Yoshida, K., Kanie, K., Shimizu, K., Honda, H., Kato, R.

    Journal of Bioscience and Bioengineering   Vol. 123 ( 5 ) page: 642-650   2017

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    Language:English   Publishing type:Research paper (scientific journal)  

  73. Optimization of Albumin Secretion and Metabolic Activity of Cytochrome P450 1A1 of Human Hepatoblastoma HepG2 Cells in Multicellular Spheroids by Controlling Spheroid Size Reviewed

    Nishikawa T, Tanaka Y, Nishikawa M, Ogino Y, Kusamori K, Mizuno N, Mizukami Y, Shimizu K, Konishi S, Takahashi Y, Takakura Y.

    Biological Pharmaceutical Bulletin   Vol. 40 ( 3 ) page: 334-338   2017

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  74. A Single Cell Culture System Using Lectin-Conjugated Magnetite Nanoparticles and Magnetic Force to Screen Mutant Cyanobacteria Reviewed

    Arai, S., Okochi, M., Shimizu, K., Hanai, T., Honda, H.

    Arai, S., Okochi, M., Shimizu, K., Hanai, T., Honda, H.   Vol. 113 ( 1 ) page: 112-119   2016

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  75. 骨格筋組織培養用マイクロ流体チップの開発 Invited

    清水一憲

    バイオサイエンスとインダストリー   Vol. 74 ( 3 ) page: 224-225   2016

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    Authorship:Lead author   Language:Japanese  

  76. Development of a tactical screening method to investigate the characteristics of functional peptides Reviewed

    Kume, A., Okochi, M., Shimizu, K., Yoshida, Y., Honda, H.

    Biotechnology and Bioprocess Engineering   Vol. 21 ( 1 ) page: 119-127   2016

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  77. Optimization of renal transfection using a renal suction-mediated transfection method in mice Reviewed

    Taniguchi, Y., Kawakami, S., Fuchigami, Y., Oyama, N., Yamashita, F., Konishi, S., Shimizu, K., Hashida, M.

    Journal of Drug Targeting   Vol. 24 ( 5 ) page: 450-456   2016

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  78. Increased insulin secretion from insulin-secreting cells by construction of mixed multicellular spheroids Reviewed

    Kusamori, K., Nishikawa, M., Mizuno, N., Nishikawa, T., Masuzawa, A., Tanaka, Y., Mizukami, Y., Shimizu, K., Konishi, S., Takahashi, Y., Takakura, Y.

    Pharmaceutical Research   Vol. 33 ( 1 ) page: 247-256   2016

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  79. Plasma-Activated Medium Selectively Eliminates Undifferentiated Human Induced Pluripotent Stem Cells Reviewed

    Matsumoto, R., Shimizu, K., Nagashima, T., Tanaka, H., Mizuno, M., Kikkawa, F., Hori, M., Honda, H.

    Regenerative Therapy   Vol. 5   page: 55-63   2016

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  80. これまでの道のりと細胞内機能性ペプチド探索技術の開発 Invited

    清水一憲

      Vol. 102   page: 8-11   2016

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  81. Microfluidic Devices for Construction of Contractile Skeletal Muscle Microtissues Reviewed

    Shimizu, K., Araki, H., Sakata, K., Tonomura, W., Hashida, M., Konishi, S.

    Journal of Bioscience and Bioengineering   Vol. 119 ( 2 ) page: 212-216   2015

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  82. Effects of the properties of short peptides conjugated with cell-penetrating peptides on their internalization into cells Reviewed

    Matsumoto, R., Okochi, M., Shimizu, K., Kanie, K., Kato, R., Honda, H.

    Scientific Reports     page: Accepted   2015

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  83. Efficient capturing of circulating tumor cells using a magnetic capture column and a size-selective filter Reviewed

    Yamamoto, S., Fei, J., Okochi, M., Shimizu, K., Yusa, A., Kondo, N., Iwata, H., Nakanishi, H., Honda, H.

    Bioprocess and Biosystems Engineering     page: Accepted   2015

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  84. Transplantation of insulin-secreting multicellular spheroids for the treatment of type 1 diabetes in mice. Reviewed

    Kusamori, K., Nishikawa, M., Mizuno, N., Nishikawa, T., Masuzawa, A., Shimizu, K., Konishi, S., Takahashi, Y., Takakura, Y.

    Journal of Controlled Release   Vol. 173 ( 10 ) page: 119-124   2014

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  85. 培養細胞・組織への機械刺激負荷マイクロデバイス

    清水一憲, 小西聡, 田谷正仁

    生物工学会誌   Vol. 92 ( 4 ) page: 157-160   2014

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  86. Neutralized nanoparticle composed of SS-cleavable and pH-activated lipid-like material as a long-lasting and liver-specific gene delivery system. Reviewed

    Ukawa, M., Akita, H., Hayashi, Y., Ishiba, R., Tange, K., Arai, M., Kubo, K., Higuchi, Y., Shimizu, K., Konishi, S., Hashida, M., Harashima, H.

    Advanced Healthcare Materials     2014

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    DOI: DOI: 10.1002/adhm.201300629

  87. Liver suction-mediated transfection in mice using a pressure-controlled computer system. Reviewed

    Shimizu, K., Zhang, G., Kawakami, S., Taniguchi, Y., Hayashi, K., Hashida, M., Konishi, S.

    Biological Pharmaceutical Bulletin   Vol. 37 ( 4 ) page: 569-575   2014

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  88. Metabolic flux analysis of genetically engineered Saccharomyces cerevisiae that produces lactate under micro-aerobic conditions. Reviewed

    Nagamori, E., Shimzu, K., Fujita, H., Tokuhiro, K., Ishida, N., Takahashi, H.

    Bioprocess and Biosystems Engineering   Vol. 36 ( 9 ) page: 1261-1265   2013

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  89. Fed-batch system for cultivating genetically engineered yeast that produces lactic acid via the fermentative promoter Reviewed

    Nagamori, E., Fujita, H., Shimizu, K., Tokuhiro, K., Ishida, N., Takahashi, H.

    Journal of Bioscience and Bioengineering   Vol. 115 ( 2 ) page: 193-195   2013

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  90. Poly(N-isopropylacrylamide)-coated microwell arrays for construction and recovery of multicellular spheroids. Reviewed

    Shimizu, K., Kusamori, K., Nishikawa, M., Mizuno, N., Nishikawa, T., Masuzawa, A., Katano, S., Takahashi, Y., Takakura, Y., Konishi, S.

    Journal of Bioscience and Bioengineering   Vol. 115 ( 6 ) page: 695-699   2013

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  91. 生細胞内の圧力を測定する

    清水一憲

    化学とマイクロ・ナノシステム学会会誌   Vol. 12 ( 2 ) page: 32   2013

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  92. MEMS技術を用いた骨格筋組織チップの開発

    清水一憲, 小西聡

    生体医工学   Vol. 51 ( 3 ) page: 207-210   2013

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  93. Evaluation systems of generated forces of skeletal muscle cell-based bio-actuators. Reviewed

    Shimizu, K., Fujita, H., Nagamori, E.

    Journal of Bioscience and Bioengineering   Vol. 115 ( 2 ) page: 115-121   2013

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  94. Investigation of denaturation of hydrophobic perfluoropolymer surfaces and their applications for micropatterns on biochip. Reviewed

    Kobayashi, T., Shimizu, K., Konishi, S.

    IEEE/ASME Journal of Micoelectromechanical Systems   Vol. 21 ( 1 ) page: 62-67   2012

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  95. In vivo site-specific transfection of naked plasmid DNA and siRNAs in mice by using a tissue suction device. Reviewed

    Shimizu, K., Kawakami, S., Hayashi, K., Kinoshita, H., Kuwahara, K., Nakao, K., Hashida, M., Konishi, S.

    PLoS ONE   Vol. 7 ( 7 ) page: e41319   2012

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  96. Implantable pneumatically actuated microsystem for renal pressure-mediated transfection in mice. Reviewed

    Shimizu, K., Kawakami, S., Hayashi, K., Mori, Y., Hashida, M., Konishi, S.

    Journal of Controlled Release   Vol. 159 ( 1 ) page: 85-91   2012

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  97. Designing of a Si-MEMS device with an integrated skeletal muscle cell-based bio-actuator. Reviewed

    Fujita, H., Dau, V.T., Shimizu, K., Hatsuda, R., Sugiyama, S., Nagamori, E.

    Biomedical Microdevices   Vol. 13 ( 1 ) page: 123-129   2011

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  98. Enhanced angiogenesis by transplantation of mesenchymal stem cell sheet created by a novel magnetic tissue engineering method. Reviewed

    Ishii, M., Shibata, R., Numaguchi, Y., Kito, T., Suzuki, H., Shimizu, K., Ito, A., Honda, H., Murohara, T.

    Arteriosclerosis, Thrombosis, and Vascular Biology   Vol. 31 ( 10 ) page: 2210-2215   2011

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  99. Development of a suction device for stabilizing in vivo real-time imaging of murine tissues. Reviewed

    Shimizu. K., Higuchi, Y., Kozu, Y., Hashida, M., Konishi, S.

    Journal of Bioscience and Bioengineering   Vol. 112 ( 5 ) page: 508-510   2011

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  100. Development of a biochip with serially connected pneumatic balloons for cell-stretching culture. Reviewed

    Shimizu, K., Shunori, A., Morimoto, K., Hashida, M., Konishi, S.

    Sensors and Actuators B: Chemical   Vol. 156 ( 1 ) page: 486-493   2011

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  101. Formation of superhydrophobic/superhydrophilic patterns by combination of nanostructure-imprinted perfluoropolymer and nanostructured silicon oxide for biological droplet generation. Reviewed

    Kobayashi, T., Shimizu, K., Kaizuma, Y., Konishi, S.

    Applied Physics Letters   Vol. 98 ( 12 ) page: 123706   2011

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  102. Novel combination of hydrophilic/hydrophobic surface for large wettability difference and its application to liquid manipulation. Reviewed

    Kobayashi, T., Shimizu, K., Kaizuma, Y., Konishi, S.

    Lab on a Chip   Vol. 11 ( 4 ) page: 639-644   2011

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  103. 生体外で生体応答を再現する

    清水一憲

    生物工学会誌   Vol. 89   page: 687   2011

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  104. 生体組織核酸導入法へのMEMS技術の応用

    清水一憲

      Vol. 27   page: 12-16   2011

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  105. Micropatterning of single myotubes on a thermoresponsive culture surface using elastic stencil membranes for single-cell analysis. Reviewed

    Shimizu, K., Fujita, H., Nagamori, E.

    Journal of Bioscience and Bioengineering   Vol. 109 ( 2 ) page: 174-178   2010

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  106. Rapid decrease in active tension generated by C2C12 myotubes after termination of artificial exercise. Reviewed

    Fujita, H., Hirano, M., Shimizu, K., Nagamori, E.

    Journal of Muscle Research and Cell Motility   Vol. 31 ( 4 ) page: 279-288   2010

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  107. Evaluation of serum-free differentiation conditions for C2C12 myoblast cells assessed as to active tension generation capability. Reviewed

    Fujita, H., Endo, A., Shimizu, K., Nagamori, E.

    Biotechnology and Bioengineering   Vol. 107 ( 5 ) page: 894-901   2010

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  108. Enhancement of C2C12 differentiation by perfluorocarbon-mediated oxygen delivery. Reviewed

    Fujita, H., Shimizu, K., Morioka, Y., Nagamori, E.

    Journal of Bioscience and Bioengineering   Vol. 110 ( 3 ) page: 359-362   2010

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  109. Novel method for measuring active tension generation by C2C12 myotube using UV-crosslinked collagen film. Reviewed

    Fujita, H., Shimizu, K., Nagamori, E.

    Biotechnology and Bioengineering   Vol. 106 ( 3 ) page: 482-489   2010

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  110. Oxygen plasma-treated thermoresponsive polymer surfaces for cell sheet engineering. Reviewed

    Shimizu, K., Fujita, H., Nagamori, E.

    Biotechnology and Bioengineering   Vol. 106 ( 2 ) page: 303-310   2010

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  111. Assembly of skeletal muscle cells on a Si-MEMS device and their generative force measurement. Reviewed

    Shimizu, K., Sasaki, H., Hida, H., Fujita, H., Obinata, K., Shikida, M., Nagamori, E.

    Biomedical Microdevices   Vol. 12 ( 2 ) page: 247-252   2010

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  112. Fabrication of scaffold-free contractile skeletal muscle tissue using magnetite-incorporated myogenic C2C12 cells. Reviewed

    Fujita, H., Shimizu, K., Yamamoto, Y., Ito, A., Kamihira, M., Nagamori, E.

    Journal of Tissue Engineering and Regenerative Medicine   Vol. 4 ( 6 ) page: 437-443   2010

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  113. Application of a cell sheet-polymer film complex with temperature sensitivity for increased mechanical strength and cell alignment capability. Reviewed

    Fujita, H.*, Shimizu, K.*, Nagamori, E.

    Biotechnology and Bioengineering   Vol. 103 ( 2 ) page: 370-377   2009

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  114. Preparation of artificial skeletal muscle tissues by a magnetic force-based tissue engineering technique. Reviewed

    Yamamoto, Y., Ito, A., Kato, M., Kawabe, Y., Shimizu, K., Fujita, H., Nagamori, E., Kamihira, M.

    Journal of Bioscience and Bioengineering   Vol. 108 ( 6 ) page: 538-543   2009

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  115. Novel method for fabrication of skeletal muscle construct from the C2C12 myoblast cell line using serum-free medium AIM-V. Reviewed

    Fujita, H., Shimizu, K., Nagamori, E.

    Biotechnology and Bioengineering   Vol. 103 ( 5 ) page: 1034-1041   2009

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  116. Alignment of skeletal muscle myoblasts and myotubes using linear micropatterned surfaces ground with abrasives. Reviewed

    Shimizu, K., Fujita, H., Nagamori, E.

    Biotechnology and Bioengineering   Vol. 103 ( 3 ) page: 631-638   2009

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  117. Effect of global transcriptional regulators related to carbohydrate metabolism on organic solvent tolerance in Escherichia coli. Reviewed

    Okochi, M., Kurimoto, M., Shimizu, K., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 105 ( 4 ) page: 389-394   2008

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  118. Construction of multi-layered cardiomyocyte sheets using magnetite nanoparticles and magnetic force. Reviewed

    Shimizu, K., Ito, A., Lee, J.K., Yoshida, T., Miwa, K., Ishiguro, H., Numaguchi, Y., Murohara, T., Kodama, I., Honda, H.

    Biotechnology and Bioengineering   Vol. 96 ( 4 ) page: 803-809   2007

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  119. Mag-seeding of rat bone marrow stromal cells into porous hydroxyapatite scaffolds for bone tissue engineering. Reviewed

    Shimizu, K., Ito, A., Honda, H.:

    Journal of Bioscience and Bioengineering   Vol. 104 ( 3 ) page: 171-177   2007

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  120. Effective cell-seeding technique using magnetite nanoparticles and magnetic force onto decellularized blood vessels for vascular tissue engineering. Reviewed

    Shimizu, K., Ito, A., Arinobe, M., Murase, Y., Iwata, Y., Narita, Y., Kagami, H., Ueda, M., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 103 ( 5 ) page: 472-478   2007

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  121. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force. Reviewed

    Shimizu, K., Ito, A., Yoshida, T., Yamada, Y., Ueda, M., Honda, H.

    Journal of Biomedical Materials Research, Part B: Applied Biomaterials   Vol. 82 ( 2 ) page: 471-480   2007

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  122. Increase of organic solvent tolerance by overexpression of manXYZ in Escherichia coli. Reviewed

    Okochi, M., Kurimoto, M., Shimizu, K., Honda, H.

    Applied Microbiology and Biotechnology   Vol. 73 ( 6 ) page: 1394-1399   2007

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  123. Enhanced cell-seeding into 3D porous scaffolds by use of magnetite nanoparticles. Reviewed

    Shimizu, K., Ito, A., Honda, H.

    Journal of Biomedical Materials Research, Part B: Applied Biomaterials   Vol. 77 ( 2 ) page: 265-272   2006

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  124. Discovery of glpC, an organic solvent tolerance-related gene in Escherichia coli, using gene expression profiles from DNA microarrays. Reviewed

    Shimizu, K., Hayashi, S., Kako, T., Suzuki, M., Tsukagoshi, N., Doukyu, N., Kobayashi, T., Honda, H.

    Applied and Environmental Microbiology   Vol. 71 ( 2 ) page: 1093-1096   2005

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  125. Magnetic force-based mesenchymal stem cell expansion using antibody-conjugated magnetoliposomes. Reviewed

    Ito, A., Hibino, E., Shimizu, K., Kobayashi T., Yamada Y., Hibi H., Ueda M., Honda H.

    Journal of Biomedical Materials Research Part B: Applied Biomaterials   Vol. 75 ( 2 ) page: 320-327   2005

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  126. Time-course data analysis of gene expression profiles reveals purR regulon concerns in organic solvent tolerance in Escherichia coli. Reviewed

    Shimizu, K., Hayashi, S., Doukyu, N., Kobayashi, T., Honda, H.

    Journal of Bioscience and Bioengineering   Vol. 99 ( 1 ) page: 72-74   2005

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  127. DNAマイクロアレイを用いた大腸菌の有機溶媒耐性関連遺伝子の探索

    清水一憲, 栗本昌樹, 林修平, 花井泰三, 大河内美奈, 小林猛, 本多裕之

    酵素工学ニュース   Vol. 53   page: 27-31   2005

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▼display all

Books 13

  1. 日本生物工学会100年史 4-4. 生体医用分野を切り拓くこれからの生物工学 医用分野における生体分子工学のこれから

    清水一憲( Role: Contributor)

    2022.4 

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    Language:Japanese

  2. 最先端ナノライフシステム研究 第II編 マイクロ・ナノメカトロニクス研究 第7章 細胞培養マイクロデバイスを用いた骨格筋モデルの開発と応用

    清水一憲、本多裕之( Role: Joint author)

    丸善プラネット  2022.3 

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    Language:Japanese

  3. 生物化学工学: バイオプロセスの基礎と応用 第2版

    小林 猛 (編集), 田谷 正仁 (編集), 本多 裕之 (著), 上平 正道 (著), 中島田 豊 (著), 境 慎司 (著), 清水 一憲 (著)( Role: Joint author)

    東京化学同人  2019 

  4. 骨格筋研究を核としたスマート筋社会・培養骨格筋細胞の張力評価技術:従来技術から最新技術

    清水一憲, 藤田英明, 本多裕之( Role: Joint author)

    シーエムシー出版  2019 

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    Language:Japanese Book type:Scholarly book

  5. 生物化学工学: バイオプロセスの基礎と応用 第2版

    小林 猛, 田谷 正仁, 本多 裕之, 上平 正道, 中島田 豊, 境 慎司, 清水 一憲( Role: Joint author)

    東京化学同人  2019 

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    Responsible for pages:1-150   Language:Japanese Book type:Textbook, survey, introduction

  6. 骨格筋研究を核としたスマート筋社会・培養骨格筋細胞の張力評価技術:従来技術から最新技術

    清水一憲, 藤田英明, 本多裕之( Role: Joint author)

    シーエムシー出版  2019 

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    Responsible for pages:127-133   Language:Japanese Book type:Scholarly book

  7. リキッドバイオプシー―体液中腫瘍マーカーの検出・解析技術―・磁気分離とサイズ選択によるCTC回収とオンフィーダー培養

    清水一憲, 本多裕之( Role: Joint author)

    シーエムシー出版  2017 

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    Language:Japanese Book type:Scholarly book

  8. 動物細胞培養の手法と細胞死・増殖不良・細胞変異を防止する技術・ 第2章第8節 電気的・機械的刺激による細胞培養を成功させる技術 [4] 培養細胞への伸展刺激負荷装置

    清水一憲, 小西聡( Role: Joint author)

    技術情報協会  2014 

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    Language:Japanese

  9. ナノバイオ技術と最新創薬応用研究, 遺伝子医学 MOOK 20号・第6章4 MEMSデバイスによる核酸デリバリー技術

    清水一憲( Role: Sole author)

    メディカル ドゥ  2012 

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    Language:Japanese

  10. 食のバイオ計測の最前線-機能解析と安全・安心の計測を目指して-・[計測開発編] 第1章 大学・研究期間の研究動向 4. バイオセンサーデバイスにおけるサンプル前処理技術

    小西聡, 小林大造, 殿村渉, 清水一憲( Role: Sole author)

    シーエムシー出版  2011 

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    Language:Japanese

  11. 未来材料・磁性ビーズを利用した細胞シートの創製

    清水一憲, 伊野浩介, 井藤彰, 本多裕之( Role: Joint author)

    エヌ・ティー・エス  2006 

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    Language:Japanese

  12. 一細胞定量解析の最前線‐ライフサーベイヤ構築に向けて・第4章 3.細胞の磁気ラベル・磁気誘導を用いた組織構築

    本多裕之, 井藤彰, 清水一憲, 伊野浩介( Role: Sole author)

    シーエムシー出版  2006 

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    Language:Japanese

  13. 化学工学シンポジウムシリーズ 79 診断・治療システムにおける化学工学・抗体結合型マグネトリポソームを用いた間葉系幹細胞の濃縮培養法

    清水一憲, 井藤彰, 日比野恵理, 小林猛, 山田陽一, 日比英晴, 上田実, 本多裕之( Role: Joint author)

    化学工学会  2005 

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    Language:Japanese

▼display all

Presentations 58

  1. Development of skeletal muscle microphysiological systems Invited International conference

    Kazunori Shimizu

    ICCP450/JSSX International Joint meeting  2023.9.26 

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    Event date: 2023.9

    Language:English  

    Country:Japan  

  2. マイクロデバイスを用いたin vitro三次元筋組織モデルの開発と応用

    清水一憲

    第21回日本再生医療学会総会  2022.3 

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    Event date: 2022.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  3. マイクロデバイス技術を用いた培養骨格筋組織の構築と利用 Invited

    清水一憲

    2022年電気化学会第89回大会  2022.3 

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    Event date: 2022.3

    Language:Japanese  

  4. Development of in vitro human skeletal muscle models using microfabricated devices Invited International conference

    Kazunori SHIMIZU

    2021 KSBB Spring Meeting and International Symposium  2021.4 

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    Event date: 2021.4

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  5. In vitro筋組織モデルの収縮力評価ツールの開発

    清水一憲

    第6回日本筋学会学術集会  2020.12.20 

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    Event date: 2020.12

  6. In vitro筋組織モデルの収縮力評価ツールの開発

    清水一憲

    第6回日本筋学会学術集会  2020.12.20 

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    Event date: 2020.12

    Language:English   Presentation type:Oral presentation (general)  

  7. 神経筋疾患研究のための共培養デバイスの開発 Invited

    清水一憲

    新学術領域「分子夾雑化学」東海地区シンポジウム  2020.10.26 

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    Event date: 2020.10

  8. 神経筋疾患研究のための共培養デバイスの開発 Invited

    清水一憲

    新学術領域「分子夾雑化学」東海地区シンポジウム  2020.10.26 

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    Event date: 2020.10

    Language:English   Presentation type:Oral presentation (general)  

  9. 微細加工デバイスを用いた培養骨格筋細胞の機能発現と評価に関する研究

    清水一憲

    第72回日本生物工学会大会  2020.9.3 

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    Event date: 2020.9

  10. 微細加工デバイスを用いた培養骨格筋細胞の機能発現と評価に関する研究

    清水一憲

    第72回日本生物工学会大会  2020.9.3 

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    Event date: 2020.9

    Language:English   Presentation type:Oral presentation (general)  

  11. 神経筋組織チップによる生体夾雑系の再構築と疾患創薬研究への応用 Invited

    清水一憲

    分子夾雑の生命化学オンラインセミナー  2020.8.27 

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    Event date: 2020.8

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  12. 神経筋組織チップによる生体夾雑系の再構築と疾患創薬研究への応用 Invited

    清水一憲

    分子夾雑の生命化学オンラインセミナー  2020.8.27 

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    Event date: 2020.8

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  13. Microdevices for drug development targetting neuromuscular disorders Invited International conference

    Kazunori Shimizu

    AJF Seminar@Bond University 

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    Event date: 2019.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  14. Microdevices for drug development targetting neuromuscular disorders Invited International conference

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    Event date: 2019.12

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Australia  

  15. 再生医療・創薬のための生物工学技術の研究開発 Invited

    清水一憲

    テクノ・シンポジウム名大 in 長野 

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    Event date: 2019.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  16. マイクロデバイスを用いたin vitro培養筋細胞・組織評価系の開発 Invited

    清水一憲、藤田英明、長森英二、本多裕之

    第2回 筋スマート社会実現コンソーシアム 講演会 

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    Event date: 2019.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  17. マイクロデバイスを利用した細胞機能評価法の開発と応用 Invited

    清水一憲

    (独)日本学術振興会 先端ナノデバイス・材料テクノロジー第151委員会 平成30年度第7回研究会 

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    Event date: 2019.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  18. ​筋萎縮治療薬開発を目指した96穴プレート筋収縮力デバイスの開発 Invited

    大隅早紀,清水一憲,本多裕之

    名古屋大学 予防早期医療創成センター 第8回ワークショップ 

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    Event date: 2019.1

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  19. 筋萎縮治療薬開発を目指した96穴プレート筋収縮力デバイスの開発 Invited International conference

    大隅早紀, 清水一憲, 本多裕之

    名古屋大学 予防早期医療創成センター 第8回ワークショップ  2019.1.29 

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    Event date: 2019.1

    Language:English   Presentation type:Oral presentation (general)  

  20. 筋萎縮モデルの収縮力を指標とした薬剤評価系の開発

    清水 一憲、弦間里歩、後藤友規、長坂すみれ、本多裕之

    名古屋大学 予防早期医療創成センター 第7回ワークショップ 

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    Event date: 2018.1

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  21. 筋萎縮モデルの収縮力を指標とした薬剤評価系の開発 International conference

    清水 一憲, 弦間里歩, 後藤友規, 長坂すみれ, 本多裕之

    名古屋大学 予防早期医療創成センター 第7回ワークショップ  2018.1.23 

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    Event date: 2018.1

    Language:English   Presentation type:Oral presentation (general)  

  22. Biomicrodevices for in vitro skeletal muscle cell-based assays Invited International conference

    Kazunori Shimizu

    Young Asian Biological Engineers' Community (YABEC 2017) 

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    Event date: 2017.10

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  23. マイクロ・ナノ技術を利用した細胞培養法の開発と応用 Invited

    清水一憲

    日本生物工学会中部支部例会 

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    Event date: 2017.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  24. Applications of Microdevices in Biomedical/Biological Engineering Invited International conference

    Kazunori Shimizu

    Tissue Microfabrication Lab Seminar 

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    Event date: 2017.8

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  25. マイクロ・ナノテクノロジーを用いた細胞培養法の開発と応用 Invited

    清水一憲

    第64回 創薬科学セミナー 

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    Event date: 2017.7

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  26. 三次元筋組織を用いたオンチップ筋萎縮モデルの開発 Invited

    清水 一憲、弦間里歩、後藤友規、本多裕之

    名古屋大学 予防早期医療創成センター 第6回ワークショップ 

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    Event date: 2017.1

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  27. プラズマ活性溶液の再生医療応用 Invited

    清水一憲

    サイエンスカフェ 

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    Event date: 2017.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  28. 神経筋疾患に対する創薬のための細胞アッセイデバイスの開発 Invited

    清水一憲

    第5回豊田理研特定課題研究 研究会&講演会 

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    Event date: 2017.1

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  29. 神経筋疾患に対する創薬のための細胞アッセイデバイスの開発 Invited International conference

    清水一憲

    第5回豊田理研特定課題研究 研究会&講演会  2017.1.8 

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    Event date: 2017.1

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  30. Selective elimination of undifferentiated human induced pluripotent stem cells using plasma-activated medium. Invited International conference

    Kazunori SHIMIZU, Ryo Matsumoto, Takunori Nagashima, Hiromasa Tanaka, Masaaki Mizuno, Fumitaka Kikkawa, Masaru Hori, Hiroyuki Honda

    Young Asian Biological Engineers' Community (YABEC 2016) 

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    Event date: 2016.10

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  31. In vitro tissue models using microscale technologies for drug development Invited International conference

    Kazunori Shimizu

    1st KIChE-SCEJ joint symposium, 2016 KIChE Autumn meeting 

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    Event date: 2016.10

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Korea, Republic of  

  32. マイクロデバイスを用いたin vivo核酸デリバリー技術の開発

    清水一憲

    第32回日本DDS学会 

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    Event date: 2016.6

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  33. 医薬品開発への応用を目指した骨格筋細胞の培養・評価技術の開発

    清水一憲

    第51回東海化学工業会賞記念講演会 

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    Event date: 2016.5

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  34. 物理刺激と機能評価のためのバイオマイクロデバイス

    清水一憲

    第2回豊田理研特定課題研究 講演会 

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    Event date: 2016.1

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  35. Magnetic Force-based Cellular Micropatterning for Analysis of Cell-cell Interactions International conference

    Yamamoto, S., Shimizu, K., Okochi, M., Honda, H.

    Asian Congress on Biotechnology 2015 (ACB2015) 

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    Event date: 2015.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Malaysia  

  36. マイクロスケール技術を利用した培養骨格筋細胞の機能制御・評価法の開発

    清水一憲

    2015年度バイオインダストリー協会賞 発酵と代謝研究奨励賞、化学・生物素材研究開発奨励賞 合同発表会 

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    Event date: 2015.10

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  37. Magnetic Micropatterning of Different Types of Cells for Analysing Their Interactions International conference

    Shimizu, K., Yamamoto, S., Okochi, M., Honda, H.

    BMES2015 

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    Event date: 2015.10

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  38. 骨格筋組織オンチップの開発

    清水一憲

    名古屋大学 予防早期医療創成センター 第5回ワークショップ 

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    Event date: 2015.8

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  39. 動く微小骨格筋組織を搭載したマイクロ流体チップの開発

    清水 一憲、本多裕之

    名古屋大学 予防早期医療創成センター 第5回ワークショップ 

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    Event date: 2015.8

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  40. Analysis of Cell-Cell Interactions Using Magnetite Nanoparticles and Magnetic Force International conference

    Shimizu, K., Yamamoto, S., Okochi, M., Honda, H.

    7th International Symposium on Microchemistry and Microsystems 

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    Event date: 2015.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  41. Gene Delivery in Mice by Computer-assisted Tissue Suction International conference

    Shimizu, K., Zhang, G., Kawakami, S., Taniguchi, Y., Hayashi, K., Hashida, M., Konishi, S.

    The 27th Annual Meeting of Japanese Association for Animal Cell Technology (JAACT2014) 

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    Event date: 2014.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  42. In vivo Tissue Suction-Mediated Transfection Method in Mice Using a Computer System for Controlling Suction Pressure Conditions International conference

    Shimizu, K., Zhang, G., Kawakami, S., Taniguchi, Y., Hayashi, K., Hashida, M., Konishi, S.

    Young Asian Biochemical Engineers' Community (YABEC 2014) 

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    Event date: 2014.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Taiwan, Province of China  

  43. In vivo遺伝子・核酸デリバリーのためのMEMSデバイスの開発

    清水一憲

    医療情報解析学セミナー 

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    Event date: 2013.8

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:長崎大学   Country:Japan  

  44. Tissue Pressure-Mediated Delivery of Nucleic Acid-Based Drugs Using MEMS Devices International conference

    Kazunori Shimizu

    The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC'13)  

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    Event date: 2013.7

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  45. 押圧/吸引圧を利用したin vivo核酸導入法へのMEMS応用

    清水一憲

    第4回 ナノバイオ創薬研究シンポジウム  

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    Event date: 2013.3

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  46. 臓器への物理刺激を利用した遺伝子導入法

    清水一憲

    第25回日本トレーニング化学会大会 

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    Event date: 2012.12

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  47. MEMSを用いたDrug deliveryとDrug discovery International conference

    清水一憲

    創薬科学セミナー 

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    Event date: 2012.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  48. Development of in vivo gene delivery methods in mice using tissue suction devices for abdominal endoscopic gene therapy. International conference

    Shimizu, K., Kawakami, S., Hayashi, K., Katano, S., Guangyuan, Z., Maekawa, D., Hashida, M., Konishi, S.

    23th 2012 IEEE International Symposium on Micro-Nano Mehatronics and Human Science (MHS2012) 

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    Event date: 2012.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  49. Contractile skeletal muscle microtissues in microchannels. International conference

    Shimizu, K., Araki, H., Tonomura, W., Hashida, M., Konishi, S.

    The 16th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS2012) 

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    Event date: 2012.10 - 2012.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  50. MEMS Devices for Delivery of Nucleic Acid-Based Drugs International conference

    Kazunori Shimizu

    2012 IEEE Nanotechnology Material and Devices Conference (IEEE-NMDC 2012) 

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    Event date: 2012.10

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:United States  

  51. A simple PDMS-based suction device for stabilizing in vivo real time fluorescence imaging of transplanted cells in live animals. International conference

    Shimizu, K., Higuchi, Y., Kozu, Y., Hashida, M., Konishi, S.

    The 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS2011) 

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    Event date: 2011.10

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  52. Mechanical stimulator of cultured vascular endothelial cell for investigation of drug permeability of blood vessel. International conference

    Shunori, A., Shimizu, K., Hashida, M., Konishi, S.

    The 16th International Conference on Solid-state Sensors, Actuators and Microsystems (Transducers'11) 

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    Event date: 2011.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:China  

  53. Gene delivery in mice using an implanted pneumatically-actuated microsystem. International conference

    Shimizu, K., Mori, Y., Hayashi, K., Shunori, A., Kawakami, S., Hashida, M., Konishi, S.

    The 24th International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2011) 

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    Event date: 2011.1

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  54. Electrophysiological recordings using spatially arranged microelectrode probes embedded into 3-D neuronal cultures. International conference

    Tonomura, W., Shimizu, K., Konishi, S.

    The 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS 2010) 

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    Event date: 2010.10

    Language:English   Presentation type:Poster presentation  

    Country:Netherlands  

  55. Strain-gradation generator using serially connected microballoons for parallel testing of cell- stretching culture. International conference

    Shimizu, K., Shunori, A., Morimoto, K., Hashida, M., Konishi, S.

    The 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS 2010) 

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    Event date: 2010.10

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  56. Novel combination of hydrophilic/hydrophobic surface for large wettability difference and its application to liquid manipulation. International conference

    Kobayashi, T., Shimizu, K., Kaizuma, Y., Konishi, S.

    The 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (microTAS 2010) 

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    Event date: 2010.10

    Language:English   Presentation type:Poster presentation  

    Country:Netherlands  

  57. 疾患・創薬研究に資する生体を模倣した新たな神経筋共培養モデルの創製 Invited

    清水一憲

    バイオインダストリー奨励賞受賞者企画講演会 第2弾 レッドバイオの新たな息吹 ~次世代創薬はじめ産業基盤の革新的変化を齎すバイオ技術研究の最前線~  2022.4.6 

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    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  58. 疾患・創薬研究に資する生体を模倣した新たな神経筋共培養モデルの創製 Invited

    清水一憲

    バイオインダストリー奨励賞受賞者企画講演会 第2弾 レッドバイオの新たな息吹 ~次世代創薬はじめ産業基盤の革新的変化を齎すバイオ技術研究の最前線~  2022.4.6 

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

▼display all

Works 13

  1. NEWS LETTER・日本化学会バイオテクノロジー部会・海外の研究室から

    2019

  2. BB Chubu・2015 年度中部支部例会開催報告

    2015

  3. 生物工学会誌・Branch Spirit, 開催報告「第4回CHUBU懇話会」& 「2015年度中部支部例会」

    2015

  4. 生物工学会誌・Branch Spirit, 開催報告「第4回CHUBU懇話会」& 「2015年度中部支部例会」

    2015

  5. BB Chubu・2015 年度中部支部例会開催報告

    2015

  6. 生物工学会誌・特集に寄せて(特集:マイクロバイオ技術の潮流と展望~動物細胞の培養・計測・評価技術への応用~)

    2014

  7. 生物工学会誌・特集に寄せて(特集:マイクロバイオ技術の潮流と展望~動物細胞の培養・計測・評価技術への応用~)

    2014

  8. 生物工学会誌・特集に寄せて(特集:実用化に資する医薬品生産培養技術の課題と展開~抗体医薬品から細胞医薬品まで~)

    2013

  9. 生物工学会誌・特集に寄せて(特集:実用化に資する医薬品生産培養技術の課題と展開~抗体医薬品から細胞医薬品まで~)

    2013

  10. 生物工学会誌・企業ポスドクを経験して

    2009

  11. 生物工学会誌・企業ポスドクを経験して

    2009

  12. 化学工学・ハチを売るビジネス

    2003

  13. 化学工学・ハチを売るビジネス

    2003

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Research Project for Joint Research, Competitive Funding, etc. 18

  1. 神経筋オルガノイドの収縮特性計測システムの開発

    2022.4 - 2023.3

    令和3年度技術開発研究助成 

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    Authorship:Principal investigator  Grant type:Competitive

  2. 植物ペプチドホルモンを利用した無機栄養吸収促進剤の開発

    2018.4 - 2019.3

    一般財団法人 東海産業技術振興財団 第30回研究助成 

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    Grant type:Competitive

  3. 神経筋疾患解析のためのOrgan-On-A-Chipの開発

    2017.12 - 2018.12

    公益財団法人カシオ科学振興財団 第35回研究助成 

    清水一憲

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    Grant type:Competitive

  4. サルコペニア創薬のための培養骨格筋組織モデルの創製

    2017.8 - 2018.7

    公益財団法人 立松財団 第25回(平成29年度) 一般研究助成 

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    Grant type:Competitive

  5. 磁性化異種微生物集団アレイを用いたエンハンサー微生物の探索

    2016.6 - 2017.3

    マッチングプランナー 平成28年度企業ニーズ解決試験 

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    Grant type:Competitive

  6. 収縮力計測可能な神経支配骨格筋組織チップの開発

    2016.4 - 2017.3

    平成27年度技術開発研究助成奨励研究助成金 

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    Grant type:Competitive

  7. ヒト骨格筋疾患モデルマイクロチップの開発に関する研究

    2014.6 - 2015.3

    2014年度(平成26年度)学術研究助成金、一般財団法人 伊藤忠兵衛基金 

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    Grant type:Competitive

  8. ヒト多能性幹細胞由来の再生医療製品製造システムの開発

    2014.4 - 2017.3

    再生医療の産業化に向けた細胞製造・加工システムの開発 

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    Grant type:Competitive

  9. 細胞培養マイクロチップを用いた廃用性筋委縮モデルの開発

    2014.4 - 2015.3

    平成26年度豊田理研スカラー、公益財団法人豊田理化学研究所 

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    Grant type:Competitive

  10. 物理刺激を用いた幹細胞の分化指向性制御技術の開発

    2013.10 - 2014.9

    平成25年度工学研究奨励援助、公益財団法人 服部報公会 

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    Grant type:Competitive

  11. メカノバイオマイクロデバイスの開発と幹細胞培養への応用

    2013.10 - 2014.3

    平成25年度未来研究ラボシステム、大阪大学基礎工学研究科 

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    Grant type:Competitive

  12. 革新的骨格筋チップの開発とその高機能化

    2013.4 - 2014.3

    平成25年度萌芽的挑戦研究事業、大阪大学 

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    Grant type:Competitive

  13. 病原性大腸菌の付着制御に向けたメカノ腸管デバイスの開発

    2013.4 - 2014.3

    A-STEP フィージビリティスタディ【FS】ステージ 探索タイプ 

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    Grant type:Competitive

  14. 腹腔内視鏡に搭載可能な組織吸引MEMSデバイスを用いた低侵襲かつ安全な新規核酸送達法の難治性腎臓・心臓疾患への応用

    2012.4 - 2014.3

    科学技術振興調整費 

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    Grant type:Competitive

  15. 低侵襲医療が可能なマイクロデバイスを用いた次世代ドラッグデリバリー技術に関する研究

    2011.4 - 2012.3

    研究助成、財団法人 昭和報公会  

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    Grant type:Competitive

  16. PDMS-pneumatic balloons for drug delivery to target tissues

    2010.7

      More details

    Grant type:Competitive

  17. 内視鏡に搭載可能なin vivo遺伝子導入法の開発

    2010.4 - 2011.3

    A-STEP フィージビリティスタディ【FS】ステージ 探索タイプ 

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    Grant type:Competitive

  18. ハイスループットな細胞伸展培養マイクロデバイスを用いた新規核酸導入法の開発

    2010.4 - 2011.3

    平成22年度京都大学若手研究者スタートアップ研究費、京都大学 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 23

  1. マイクロデバイスを用いた微小環境精密制御による筋オルガノイド機能発現と病態解析

    Grant number:23K17474  2023.6 - 2026.3

    科学研究費助成事業  挑戦的研究(開拓)

    清水 一憲, 秋山 裕和

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    Authorship:Principal investigator 

    Grant amount:\26000000 ( Direct Cost: \20000000 、 Indirect Cost:\6000000 )

    オルガノイド(幹細胞を用いて作製した生体器官に類似した培養立体組織)は、平面培養細胞や動物実験に代わる技術として、病気の研究や薬の開発に利用することが期待されています。本研究では、マイクロデバイス技術を活用してオルガノイド機能発現を誘導し、それを用いて疾患解析を行うことを目的としています。

  2. Development of Co-Differentiation Process of Pluripotent Stem Cells for Next-Generation Regenerative Medicine

    Grant number:23K04505  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Coinvestigator(s) 

  3. Establishment of efficient exploring method for non-inferior bioactive peptides from edible proteins

    Grant number:22H00273  2022.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

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    Authorship:Coinvestigator(s) 

  4. 環境/遺伝要因による神経筋疾患チップの創製と疾患創薬研究への応用

    Grant number:22H01878  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    清水 一憲

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    Authorship:Principal investigator 

    Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )

    本研究では、申請者が最近開発した運動神経細胞と骨格筋細胞の共培養マイクロデバイスである神経筋チップ(第一世代)を基盤に、高精度・高感度な神経筋チップ(第二世代)を開発する。さらに、開発した第二世代チップを利用し、疾患状態を模倣した神経筋疾患チップを創製し、疾患創薬研究を行う。疾患チップの特徴を活用することで従来法では不可能なアプローチで環境要因疾患と遺伝要因疾患の疾患解析や治療法開発を進める。

  5. Improved understanding and application development of innovative organoid formation process by mechanical stress control

    Grant number:21K19899  2021.7 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Shimizu Kazunori

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    Authorship:Principal investigator 

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    In this study, we aimed to control human iPS cell-derived neuromuscular organoid formation using microdevices to better understand the process and apply it to the development of innovative nonclinical testing techniques. We found that increasing cell density, decreasing well size, and adding ROCK inhibitors increased the contractility of muscle tissue. We also suggested that a neuromuscular junction exists within the neuromuscular organoids and contains Schwann cells and other cells. We attempted to further improve the efficiency of neuromuscular junction formation in order to develop a robust test method, but no significant increase was observed. In the future, it may be possible to increase neuromuscular junction formation by further enhancing myocyte maturation.

  6. Secretory Characteristics and Functions of Exercise EVs for the Creation of Innovative Exercise Medicine

    Grant number:21K18848  2021.7 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Honda Hiroyuki

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    Authorship:Coinvestigator(s) 

    It is not clear how exercise alters the number and quality of EVs secreted by skeletal muscle cells. In this study, we used an in vitro exercise model to examine whether exercise affects the amount of EVs released from skeletal muscle cells. The effects of 1 Hz and 30 Hz electrical stimulation applied under different exercise conditions for 24 hours were examined. The results showed that the amount of EVs secreted increased and the type of mircoRNAs contained in EVs also fluctuated when the subjects were exercised with 30 Hz electrical stimulation. Furthermore, it was suggested that changes in Alix expression and calcium ion concentration were involved in this.

  7. 神経筋組織チップによる生体夾雑系の再構築と疾患創薬研究への応用

    Grant number:20H04705  2020.4 - 2022.3

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    清水 一憲

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    Authorship:Principal investigator 

    Grant amount:\4940000 ( Direct Cost: \3800000 、 Indirect Cost:\1140000 )

    様々な神経筋疾患により、運動ニューロンや神経筋シナプスが機能不全に陥ると、筋細胞を動かすことができない。その結果、筋萎縮や筋力低下が起こり、場合によって死に至る。多くの神経筋疾患の発症機構は未解明であり、有効な治療法がない。研究代表者はこれまでに神経筋疾患の研究・創薬のためのマイクロデバイスの開発を進めてきた。本研究では、開発を進めてきた神経筋組織チップを完成させ、球脊髄性筋萎縮症(SBMA)患者由来iPS細胞を用いてSBMA神経筋組織チップを構築し、病態再現と分子病態解明を行うとともに、治療薬探索のための基盤技術を確立する。

  8. Development of 3D cultured skeletal muscle tissue for elucidation of molecular mechanisms of muscle aging

    Grant number:19K11369  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KISHIDA TSUNAO

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    Authorship:Coinvestigator(s) 

    The goal of this study is to establish a fundamental technology that contribute to the elucidation of the molecular mechanisms of sarcopenia. Myoblasts were seeded in a fibrin-based gel, and three-dimensional muscle tissue was formed by several days of differentiation culture using differentiation induction medium. Immunostaining revealed numerous myotubular cells that possess sarcomere structures. An electrical stimulation resulted in contraction of the 3D muscle tissue. The tension generated by the electro-stimulated muscle tissue was measured using a contraction force measurement microdevice, showing that the contraction force tended to increase during the culture period.

  9. 筋老化の分子機構解明のための3D培養骨格筋組織の開発

    2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    岸田綱郎

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    Grant type:Competitive

  10. モザイク状培養筋組織モデルの開発

    2018.4 - 2022.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator 

  11. 神経筋疾患解析のためのOrgan-On-A-Chipの開発

    2017.12 - 2018.12

    公益財団法人カシオ科学振興財団  公益財団法人カシオ科学振興財団 第35回研究助成 

    清水一憲

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    Grant type:Competitive

  12. 新奇な細胞応答性の違いを利用した細胞分離法の開発とそのメカニズム解明

    2017.7 - 2019.3

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

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    Grant type:Competitive

  13. Development of a cell separation method using medium with high concentration of amino acids

    Grant number:17K19010  2017.6 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Shimizu Kazunori

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    Authorship:Principal investigator 

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    In this study, we aimed to developed a selective removal method for undifferentiated iPSCs using a high-concentration amino acid-added solution and clarify the cell response mechanism. Undifferentiated iPSCs and differentiated cells including human primary cells and iPSC-derived cells were used. As a result of conducting experiments by changing the concentration and the exposure time, it was found that the undifferentiated iPSC cells can be efficiently and selectively removed by exposing to a medium containing 1.2 mol / l L-alanine for 2 hours. We conducted experiments using various media components, L-alanine isomers, temperature, and inhibitors of endocytosis, and proposed a hypothesis of a cell response mechanism.

  14. Development of skeletal muscle-on- a-chip for investigating cell-cell/cell-ECM interaction(Fostering Joint International Research)

    Grant number:16KK0126  2017 - 2019

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Fund for the Promotion of Joint International Research (Fostering Joint International Research)

    Shimizu Kazunori

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    Authorship:Principal investigator 

    Grant amount:\15080000 ( Direct Cost: \11600000 、 Indirect Cost:\3480000 )

    In this study, we improved the tissue chip capable of measuring contractile force and constructed muscle tissues with a vascular-like structure capable of perfusion. A vessel-like structure was constructed in muscle tissues using C2C12, HUVEC and fibrin gel. The cultured muscle tissue with vascular-like structure contracted in response to electrical stimulation and the culture medium was able to be perfused in the vascular-like structure of the tissues.

  15. The design of the cell internal division child confirmation peptide and cell function alteration

    Grant number:16H04575  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    HONDA HIROYUKI

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    Authorship:Coinvestigator(s) 

    Peptides that have biological activities are called functional peptides. Many types of functional peptides have been found to date and has been designed for development of peptide drug. In the present study, following 3 topics were investigated, 1) fabrication of peptide library including unnatural amino acid, 2) screening of intracellular functional peptide conjugated with cell penetrating peptide (CPP), 3) development of the smart machinery for removal of CPP in intracellular space. Related to the last topic, we have established the methodology for disulfide bond formation of all peptides on peptide array. In addition, we have been developed a novel synthesis method of hetero-dimerized peptide using intramolecular disulfide bonding between main- and sub-chain of lysin.

  16. メゾスケール空間内移動速度論創成のための挑戦的研究

    2015.4 - 2017.3

    科学研究費補助金  挑戦的萌芽研究

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    Authorship:Coinvestigator(s) 

  17. Development of in vitro skeletal muscle tissue models and their application as atrophy models for drug development

    Grant number:26709062  2014.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (A)

    Shimizu Kazunori

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    Authorship:Principal investigator 

    Grant amount:\24440000 ( Direct Cost: \18800000 、 Indirect Cost:\5640000 )

    In this study, we developed cell assay technology for muscle atrophy. We developed a skeletal muscle tissue chip with a 3D muscle tissue on a microdevice and developed a muscle atrophy model by inducing atrophy to it. Specifically, we succeeded in constructing a three-dimensional tissue that contracts in response to electrical stimulation using mouse and human skeletal muscle cells. We found that the muscle atrophy-related genes were highly expressed and their contractile power significantly decreased by adding the compound to the culture medium of those tissues. Furthermore, we showed that the developed muscle atrophy model was capable of searching for substances that suppress the decrease in contractile force.

  18. 磁性ナノテクノロジーによる骨格筋再生医療の技術基盤の創製

    2014.4 - 2017.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Coinvestigator(s) 

  19. 組織押圧・吸引圧を利用した遺伝子導入システムの開発

    2014.4 - 2017.3

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

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    Grant type:Competitive

  20. 磁性ナノテクノロジーによる骨格筋再生医療の技術基盤の創製

    2014.4 - 2017.3

    日本学術振興会  科学研究費補助金  基盤研究(B)

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    Authorship:Coinvestigator(s)  Grant type:Competitive

  21. オンチップ神経支配筋組織の創製

    2014.4 - 2016.3

    科学研究費補助金  挑戦的萌芽研究

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    Authorship:Principal investigator 

  22. 細胞伸展培養用マイクロデバイスを用いた組織押圧核酸導入法のメカニズム解明

    2011.4 - 2013.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  23. 磁力を用いたヒト培養細胞のポジショニングと組織的細胞集合体の構築

    2006.4 - 2007.3

    科学研究費補助金 

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    Authorship:Principal investigator 

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Industrial property rights 22

  1. 共培養用デバイス、運動神経細胞培養用デバイス、神経筋疾患のin vitro評価モデルの作製方法、および、神経筋疾患の治療薬のスクリーニング方法

    清水一憲,本多裕之,山岡奈央

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    Application no:特願2019-28451  Date applied:2019.2

    Country of applicant:Domestic  

  2. 共培養用デバイス、運動神経細胞培養用デバイス、神経筋疾患のin vitro評価モデルの作製方法、および、神経筋疾患の治療薬のスクリーニング方法

    清水一憲, 本多裕之, 山岡奈央

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    Application no:特願2019-28451  Date applied:2019.2

    Country of applicant:Domestic  

  3. 苦味ペプチド除去剤、食品又は医薬品の製造方法、及び苦味ペプチドを除去する方法

    本多裕之、清水一憲、今井健人、池田彩、上村光浩、小川光輝

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    Application no:特願2018-143822  Date applied:2018.7

    Country of applicant:Domestic  

  4. 苦味ペプチド除去剤、食品又は医薬品の製造方法、及び苦味ペプチドを除去する方法

    本多裕之, 清水一憲, 今井健人, 池田彩, 上村光浩, 小川光輝

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    Application no:特願2018-143822  Date applied:2018.7

    Country of applicant:Domestic  

  5. 基質分解活性の評価方法

    清水一憲、石原真以、本多裕之

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    Application no:特願2018-037098  Date applied:2018.3

    Country of applicant:Domestic  

  6. 基質分解活性の評価方法

    清水一憲, 石原真以, 本多裕之

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    Application no:特願2018-037098  Date applied:2018.3

    Country of applicant:Domestic  

  7. プロテアーゼの切断性評価

    本多裕之、加藤竜司、清水一憲

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    Application no:特願2017-150361  Date applied:2017.8

    Country of applicant:Domestic  

  8. プロテアーゼの切断性評価

    本多裕之, 加藤竜司, 清水一憲

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    Application no:特願2017-150361  Date applied:2017.8

    Country of applicant:Domestic  

  9. 未分化多能性幹細胞の選択的な除去

    清水一憲、本多裕之、長島拓則

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    Application no:特願2017-149479  Date applied:2017.8

    Country of applicant:Domestic  

  10. 未分化多能性幹細胞の選択的な除去

    清水一憲, 本多裕之, 長島拓則

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    Application no:特願2017-149479  Date applied:2017.8

    Country of applicant:Domestic  

  11. タンパク質又はペプチドの酵素切断部位検出方法

    本多裕之、清水一憲、越智浩、栗本昌樹

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    Application no:特願2017-146141  Date applied:2017.7

    Country of applicant:Domestic  

  12. タンパク質又はペプチドの酵素切断部位検出方法

    本多裕之, 清水一憲, 越智浩, 栗本昌樹

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    Application no:特願2017-146141  Date applied:2017.7

    Country of applicant:Domestic  

  13. 体内輸送担体及びこれを用いた複合体

    上村光浩、小川光輝、本多裕之、清水一憲、今井健人

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    Application no:特願2017-92447  Date applied:2017.5

    Country of applicant:Domestic  

  14. 体内輸送担体及びこれを用いた複合体

    上村光浩, 小川光輝, 本多裕之, 清水一憲, 今井健人

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    Application no:特願2017-92447  Date applied:2017.5

    Country of applicant:Domestic  

  15. 微生物の共培養法

    清水一憲,本多裕之,鈴木宏昭,酒井香苗,河合盛進

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    Application no:特願2016-185171  Date applied:2016.9

    Country of applicant:Domestic  

  16. 分化細胞の生産方法およびiPS細胞の未分化細胞の除去方法

    本多裕之, 清水一憲, 松本凌, 堀勝, 水野正明, 吉川史隆, 田中宏昌

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    Application no:特願2015-155312  Date applied:2015.8

    Country of applicant:Domestic  

  17. 生体試料固定器

    樋口ゆり子, 清水一憲, 小西聡, 橋田充

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    Applicant:国立大学法人京都大学, 学校法人立命館

    Application no:特願2011-259007  Date applied:2011.11

    Patent/Registration no:特許第5930364号  Date registered:2016.5 

    Country of applicant:Domestic  

  18. 筋細胞の出力装置及び筋細胞の出力評価方法

    藤田英明, 清水一憲, 長森英二

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    Applicant:株式会社豊田中央研究所

    Application no:特願2010-247914  Date applied:2010.11

    Patent/Registration no:特許第5549547号  Date registered:2014.5 

    Country of applicant:Domestic  

  19. 導入対象物質の送達装置の作動方法および導入対象物質の送達方法(PCT)

    清水一憲, 小西聡, 川上茂, 橋田充

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    Applicant:国立大学法人京都大学, 学校法人立命館

    Application no:特願2010-238885  Date applied:2010.10

    Country of applicant:Domestic  

  20. Cell culture support and production method and uses thereof

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    Application no:12/659120  Date applied:2010.2

    Announcement no:US 2010/0216242 

    Country of applicant:Foreign country  

  21. 細胞培養担体及びその利用

    清水一憲, 藤田英明, 長森英二

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    Applicant:株式会社豊田中央研究所

    Application no:特願2009-132301  Date applied:2009.6

    Patent/Registration no:特許第4483994号  Date registered:2010.4 

    Country of applicant:Domestic  

  22. 培養細胞のハンドリング体、その製造方法及びその利用

    藤田英明, 清水一憲, 長森英二

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    Applicant:株式会社豊田中央研究所

    Application no:特願2008-180547  Date applied:2008.7

    Patent/Registration no:特許第4553038号  Date registered:2010.7 

    Country of applicant:Domestic  

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Teaching Experience (On-campus) 34

  1. 生命化学1及び演習

    2022

  2. 生命化学3及び演習

    2022

  3. 実験安全学

    2020

  4. 化学工学基礎

    2020

  5. 生命システム工学セミナー

    2020

  6. 生命システム工学セミナー

    2019

  7. 化学生命工学実験3

    2019

  8. 医工連携セミナー

    2019

  9. Core-Biochemistry

    2019

  10. 生物化学工学

    2019

  11. 生命システム工学基礎論

    2019

  12. 化学生命工学実験2

    2019

  13. 生化学IV及び演習

    2019

  14. 生物化学工学

    2017

  15. 化学工学基礎

    2017

  16. 生物プロセス工学

    2017

  17. 生命システム工学セミナー

    2017

  18. Core Biochemistry

    2017

  19. 生命システム工学基礎論

    2017

  20. 生物化学工学

    2017

  21. 理系基礎化学実験

    2016

  22. 生物プロセス工学

    2016

  23. 化学工学基礎

    2016

  24. バイオテクノロジーセミナー

    2016

  25. バイオテクノロジー基礎論

    2016

  26. 生物化学工学

    2016

  27. 実験安全学

    2016

  28. 生物化学工学特論

    2015

  29. バイオテクノロジー基礎論

    2015

  30. バイオテクノロジーセミナー

    2015

  31. 生物プロセス工学

    2015

  32. 化学工学基礎

    2015

  33. 生物化学工学

    2015

  34. 生物化学工学

    2014

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Teaching Experience (Off-campus) 2

  1. 生命システム工学セミナー

    2020 Nagoya University)

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    Level:Postgraduate 

  2. 実験安全学

    2020 Nagoya University)

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    Level:Undergraduate (specialized) 

 

Media Coverage 17

  1. L-アンセリンはヒト由来培養筋組織の収縮力を向上させる~サルコペニア予防に寄与する成分を独自の評価系で発見~

    2023.6

  2. ヒトiPS細胞から簡便かつ高効率な骨格筋分化誘導法を開発~病態の解明、新しい治療法開発の促進に期待~ Internet

    2023.5

  3. 植物の細胞を培養し、経時的な観察を可能にするマイクロデバイスの開発に成功! Internet

    日本の研究.com  2022.4

  4. 食品や化粧品業界の素材開発に新材料! 独自開発の「高温焼成シリカゲル」で、抗菌ペプチド見つかる Internet

    日本の研究.com  2021.12

  5. 愛情ホルモンで知られる「オキシトシン」の新規アンタゴニストを発見 ~新規の早産治療薬開発やオキシトシンの進化・構造解明に期待~ Internet

    日本の研究.com  2021.11

  6. 運動ニューロンからの信号で動く筋組織を再現 ~ALS などの神経筋疾患の治療法開発に期待~

    日本の研究.com  2021.4

  7. 見出し「名大、天然ペプチド発見、血糖値安定に寄与、健康食品開発目指す」 Newspaper, magazine

    日刊工業新聞  25面  2021.3

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    Author:Other 

  8. 見出し「名大、天然ペプチド発見、血糖値安定に寄与、健康食品開発目指す」 Newspaper, magazine

    日刊工業新聞  25面  2021.3

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    Author:Other 

  9. 見出し「筋肉への信号伝達iPSで再現」 Newspaper, magazine

    日経産業新聞  8面  2020.2

  10. 見出し「筋肉への信号伝達iPSで再現」 Newspaper, magazine

    日経産業新聞  8面  2020.2

  11. アカデミアや企業、残存未分化iPS細胞の除去や検出技術を続々発表 Internet

    日経バイオテク法人版onlinePharmaBusiness  2018.3

  12. アカデミアや企業、残存未分化iPS細胞の除去や検出技術を続々発表 Internet

    日経バイオテク法人版onlinePharmaBusiness  2018.3

  13. 見出し「未成長iPS簡単排除」 Newspaper, magazine

    日経産業新聞  8面  2017.10

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    Author:Other 

  14. 見出し「未成長iPS簡単排除」 Newspaper, magazine

    日経産業新聞  8面  2017.10

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    Author:Other 

  15. 見出し「ALS 体外で再現 名古屋大 難病治療へ装置開発」 Newspaper, magazine

    日経産業新聞  8面  2017.6

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    Author:Other 

  16. 見出し「ALS 体外で再現 名古屋大 難病治療へ装置開発」 Newspaper, magazine

    日経産業新聞  8面  2017.6

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    Author:Other 

  17. 見出し「体液中のがん細胞検出」 Newspaper, magazine

    日本経済新聞  15面  2015.12

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    Author:Other 

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