Faculty Profiles - ITO Akira

Papers - ITO Akira

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Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation Reviewed Open Access

Taisei Wakabayashi, Masahiro Kaneko, Tomoki Nakai, Masanobu Horie, Hiroyuki Fujimoto, Maazumi Takahashi, Shota Tanoue, Akira Ito

Bioengineering & Translational Medicine 2022.9

Immunomodulation of melanoma by chemo-thermo-immunotherapy using conjugates of melanogenesis Substrate NPrCAP and magnetite nanoparticles: a review Invited Reviewed Open Access

Yasuaki Tamura, Akira Ito, Kazumasa Wakamatsu, Takafumi Kamiya, Toshihiko Torigoe, Hiroyuki Honda, Toshiharu Yamashita, Hisashi Uhara, Shosuke Ito, Kowichi Jimbow

International Journal of Molecular Sciences Vol. 23 ( 12 ) page： 6457 2022.6

Hypoxia-responsive expression of vascular endothelial growth factor for induction of angiogenesis in artificial three-dimensional tissues. Reviewed

Shinya Masumoto, Akihiko Ono, Akira Ito, Yoshinori Kawabe, Masamichi Kamihira

Journal of Bioscience and Bioengineering Vol. 132 ( 4 ) page： 399 - 407 2021.10

Contractile activity of myotubes derived from human induced pluripotent stem cells: A model of duchenne muscular dystrophy Reviewed International journal Open Access

Kantaro Yoshioka, Akira Ito, Masanobu Horie, Kazushi Ikeda, Sho Kataoka, Keiichiro Sato, Taichi Yoshigai, Hidetoshi Sakurai, Akitsu Hotta, Yoshinori Kawabe, Masamichi Kamihira

Cells Vol. 10 ( 10 ) page： 2556 2021.10

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

Duchenne muscular dystrophy (DMD) is a genetic disorder that results from deficiency of the dystrophin protein. In recent years, DMD pathological models have been created using induced pluripotent stem (iPS) cells derived from DMD patients. In addition, gene therapy using CRISPR-Cas9 technology to repair the dystrophin gene has been proposed as a new treatment method for DMD. However, it is not known whether the contractile function of myotubes derived from gene-repaired iPS cells can be restored. We therefore investigated the maturation of myotubes in electrical pulse stimulation culture and examined the effect of gene repair by observing the contractile behaviour of myotubes. The contraction activity of myotubes derived from dystrophin-gene repaired iPS cells was improved by electrical pulse stimulation culture. The iPS cell method used in this study for evaluating muscle contractile activity is a useful technique for analysing the mechanism of hereditary muscular disease pathogenesis and for evaluating the efficacy of new drugs and gene therapy.

DOI： 10.3390/cells10102556

Development of a genetically modified hepatoma cell line with heat-inducible high liver function. Reviewed International journal Open Access

Hiroyuki Kitano, Yuki Nagae, Yoshinori Kawabe, Akira Ito, Masamichi Kamihira

Cytotechnology Vol. 73 ( 3 ) page： 353 - 362 2021.6

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

Hepatoma cells are a promising cell source for the construction of bioartificial liver (BAL) systems owing to their high proliferative capability. However, their low liver function compared with primary hepatocytes is a major problem. In a previous study, we established a genetically modified hepatoma cell line, Hepa/8F5, in which eight liver-enriched transcription factor (LETF) genes were transduced into mouse hepatoma Hepa1-6 cells using a drug-inducible transactivator system. These cells proliferate actively under normal culture conditions, meaning that large quantities can be prepared easily. When the overexpression of the LETFs is induced by the addition of an inducer drug, cell growth stops and cell morphology changes with concomitant high expression of liver functions. However, the liver functions largely depend on the presence of the inducer drug, which must be continuously added to maintain these enhanced functions. In the present study, we attempted to modify the method of induction of LETF overexpression in Hepa/8F5 cells to remove the requirement for continual drug addition. To this end, we constructed a system in which the artificial transactivator was transcribed and amplified under the control of a heat-shock protein promoter, and introduced the system into the genome of Hepa/8F5 cells. In our modified cell line, heat-triggered LETF expression was confirmed to induce high liver function. After drug-screening of transfected cells, we established a hepatoma cell line (Hepa/HS), which exhibited high, heat-inducible liver functions. The Hepa/HS cells may represent a new cell source for hepatic studies such as the construction of BAL systems. Supplementary Information: The online version of this article (10.1007/s10616-021-00457-4) contains supplementary material, which is available to authorized users.

DOI： 10.1007/s10616-021-00457-4

Web of Science

Scopus

PubMed

Miniaturized skeletal muscle tissue fabrication for measuring contractile activity. Reviewed

Kantaro Yoshioka, Akira Ito, Md Arifuzzaman, Taichi Yoshigai, Fangming Fan, Kei-Ichiro Sato, Kazunori Shimizu, Yoshinori Kawabe, Masamichi Kamihira

Journal of bioscience and bioengineering Vol. 131 ( 4 ) page： 434 - 441 2021.4

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

The contractile function of skeletal muscle is essential for maintaining the vital activity of life. Muscular diseases such as muscular dystrophy severely compromise the quality of life of patients and ultimately lead to death. There is therefore an urgent need to develop therapeutic agents for these diseases. In a previous study, we showed that three-dimensional skeletal muscle tissues fabricated using the magnetic force-based tissue engineering technique exhibited contractile activity, and that drug effects could be evaluated based on the contractile activity of the skeletal muscle tissues. However, the reported method requires a large number of cells and the tissue preparation procedure is complex. It is therefore necessary to improve the tissue preparation method. In this study, a miniature device made of polydimethylsiloxane was used to simplify the production of contracting skeletal muscle tissues applicable to high-throughput screening. The effects of model drugs on the contractile force generation of skeletal muscle tissues prepared from mouse C2C12 myoblast and human induced pluripotent stem cells were evaluated using the miniature muscle device. The results indicated that the muscle device system could provide a useful tool for drug screening.

DOI： 10.1016/j.jbiosc.2020.11.014

Web of Science

Scopus

PubMed

Magnetically triggered transgene expression system using magnetic nanoparticles Invited Reviewed Open Access

Akira Ito

Drug Delivery System 2021

LINE-1 vectors mediate recombinant antibody gene transfer by retrotransposition in Chinese hamster ovary cells. Reviewed

Feiyang Zheng, Yoshinori Kawabe, Mai Murakami, Mamika Takahashi, Kyoka Nishihata, Souichiro Yoshida, Akira Ito, Masamichi Kamihira

Biotechnology Journal Vol. 16 ( 7 ) page： 2000620 2021

Intramyocardial Transplantation ofHuman iPS Cell–Derived CardiacSpheroids Improves Cardiac Function inHeart Failure Animals. Reviewed

JACC: Basic to Translational Science Vol. 36 ( 4 ) page： 101 - 108 2021

Magnetically triggered transgene expression system using magnetic nanoparticles Open Access

Ito Akira

Drug Delivery System Vol. 36 ( 3 ) page： 175 - 184 2021

Language：Japanese Publisher：THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

Remote control of transgene expression by physical stimuli may provide a new approach for the controlled expression of therapeutic genes in cancer therapy and regenerative medicine. In this article, new approaches which use local heating of magnetic nanoparticles to transform magnetic signals into cell stimuli for gene expression are reviewed and discussed. By applying a synthetic biological approach, heat-inducible transgene expression systems are applied to target cells. The functionalized magnetite nanoparticles target cells to magnetically label them. Transgenic cells labeled with magnetite nanoparticles can express the transgene upon exposure to an alternating magnetic field. This approach may be applicable to the development of new gene therapies in cancer therapy and regenerative medicine based on the remote manipulation of cell function via transgene expression in a spatiotemporal manner.

DOI： 10.2745/dds.36.175

Open Access

Scopus

CiNii Research

Heat dose based large tumor treatment with multiple site injections of heat-generating nanoparticles dispersible within tumor tissue Reviewed

2. Tomio Morino, Akira Ito, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Takahiro Yasui

Thermal Medicine Vol. 36 ( 4 ) page： 104 - 108 2020.12

Heat Dose Based Large Tumor Treatment with Multiple Site Injections of Heat-generating Nanoparticles Dispersible within Tumor Tissue Open Access

MORINO TOMIO, ITO AKIRA, ETANI TOSHIKI, NAIKI TAKU, KAWAI NORIYASU, YASUI TAKAHIRO

Thermal Medicine Vol. 36 ( 4 ) page： 101 - 108 2020.12

Language：English Publisher：Japanese Society for Thermal Medicine

Solid cancer therapy based on necrosis induction with heat-generating nanoparticles has been developed in Japan. Heat was induced from intratumorally injected magnetite cationic lipid composite particles (MCL particles) by alternating magnetic field irradiations to kill cancer cells nearby located. In our previous report we have showed importance of heat dose index in vivo (J/cm3 tumor volume) for tumor regression when 45 mg MCL particles were injected at a single site of 1.36 cm3 tumor. Purpose of this study is to show rationale and utility of multiple site injections of MCL particles for treatment of large tumors more than 1.36 cm3.Rat mammary tumors were induced by 7,12-dimethylbenz［a］anthracene (DMBA) and tumors in range of 2.19 ～ 3.81 cm3 were applied to treatment experiment. Treatment condition was designed to reproduce the heat generation condition of the 1.36 cm3 tumor treatment at every multiple injection site in rat mammary tumors. Tumor volume divided by number of injection sites (cm3/site) was set to close to 1.36 cm3/site and 45 mg MCL particles were administered at multiple sites to keep even spaces among injection sites. Three irradiation conditions were set to give close heat dose in vivo (J/cm3) of the 1.36 cm3 tumor treatment. Treatment under designed conditions resulted in complete regression of rat tumors at 21 days after the treatment, showing theoretical validity of design procedures for the multiple site injections. Novel concept of necrosed tumor volume from an injection site (cm3/site) and its actual value under a standard injection condition of 45 mg-MCL/site were described and its use in clinic was discussed.

DOI： 10.3191/thermalmed.36.101

Open Access

CiNii Research

ハイパーサーミアの新展開 -基礎医学・臨床応用に関する最近の進歩- Reviewed

近藤隆、鈴木文男、水上達治、斎藤淳一、河合憲康、井藤　彰

放射線生物研究 Vol. 55 ( 3 ) page： 210 - 228 2020.9

Magnetic heating of nanoparticles as a scalable cryopreservation technology for human induced pluripotent stem cells Open Access

Ito, A; Yoshioka, K; Masumoto, S; Sato, K; Hatae, Y; Nakai, T; Yamazaki, T; Takahashi, M; Tanoue, S; Horie, M

SCIENTIFIC REPORTS Vol. 10 ( 1 ) page： 13605 2020.8

Language：English Publisher：Scientific Reports

Scale-up of production is needed for industrial applications and clinical translation of human induced pluripotent stem cells (hiPSCs). However, in cryopreservation of hiPSCs, successful rewarming of vitrified cells can only be achieved by convective warming of small volumes (generally 0.2 mL). Here, we present a scalable nano-warming technology for hiPSC cryopreservation employing inductive heating of magnetic nanoparticles under an alternating magnetic field. The conventional method by water bath heating at 37 °C resulted in a decrease of cell viability owing to devitrification caused by slow warming of samples with large volumes (≥ 20 mL). Nano-warming showed uniform and rapid rewarming of vitrified samples and improved viability of hiPSCs in the 20-mL system. In addition to single cells, hiPSC aggregates prepared using a bioreactor-based approach were successfully cryopreserved by the nano-warming technique. These results demonstrate that nano-warming is a promising methodology for cryopreservation in mass production of hiPSCs.

DOI： 10.1038/s41598-020-70707-6

Heat Dose Index in vivo for Cancer Therapy Using Heat-generating Nanoparticles Named Magnetite Cationic Liposomes and Alternating Magnetic Field Irradiator Open Access

MORINO TOMIO, TANOUE SHOTA, MIYATA SHUICHIRO, HIRAYAMA KOTARO, ITO AKIRA, ETANI TOSHIKI, NAIKI TAKU, KAWAI NORIYASU, YASUI TAKAHIRO

Thermal Medicine Vol. 36 ( 2 ) page： 47 - 58 2020.7

Language：English Publisher：Japanese Society for Thermal Medicine

Cancer clinical research using heat-generating nanoparticles named magnetite cationic liposomes (MCL) and alternating magnetic field (AMF) irradiator has been conducted. Heat generation from intratumorally injected MCL particles was triggered by AMF irradiation to kill cancer cells nearby located. Tumor temperature was monitored as index to control treatment condition but efficacy was variable from complete regression to ineffective. In order to improve efficacy, we have proposed novel index of heat dose in vivo (J/cm3 tumor volume). Purpose of this study was to reveal actual heat dose in vivo and discuss its utility as index.In order to enable to estimate heat dose, heat generation activity of MCL particles (J/g-MCL・min) was measured under various AMF irradiation conditions by changing output power (kW) and distance from irradiation surface (mm). Treatment condition for complete regression of animal tumors with 7 mm diameter was reproduced and heat dose in vivo (J/cm3) was calculated by multiplying heat generation activity (J/g-MCL・min) with MCL dosage (g-MCL/cm3) and irradiation time (min). Heat dose for tumor regression was revealed around 700-850 J/cm3 in every thrice AMF irradiations of a course. Since temperature-based treatments of large tumors were reported to fall into insufficiency, revealed heat dose was applied to design treatment condition of large tumor with 13-16 mm diameter, and complete regression was achieved by a course treatment. MCL dosage of temperature-based condition was found far lower than that of heat dose. Low MCL dosages (g-MCL/cm3) would cause shortage of heat dose (J/cm3) and insufficient anticancer activity, although tumor temperature could be raised by heat transfer to monitoring sites. These results showed utility of heat dose in vivo as index to ensure clinical efficacy and concomitantly to make useless invasive probe for temperature monitoring. Procedure to design treatment condition and required performance of AMF irradiator were described.

DOI： 10.3191/thermalmed.36.47

Open Access

CiNii Research

若手化学工学者としての私の履歴書 Invited Reviewed Open Access

井藤　彰

学術の動向 Vol. 25 ( 7 ) page： 98 - 102 2020.7

A Curriculum Vitae of Mine as a Chemical Engineer Open Access

ITO Akira

TRENDS IN THE SCIENCES Vol. 25 ( 7 ) page： 7_98 - 7_102 2020.7

Heat dose index in vivo for cancer therapy using heat-generating nanoparticles named magnetite cationic liposomes and alternating magnetic field irradiator Reviewed

Tomio Morino, Shota Tanoue, Shuichiro Miyata, Kotaro Hirayama, Akira Ito, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Takahiro Yasui

Vol. 36 ( 2 ) page： 47 - 58 2020.7

Novel neuromuscular junction model in 2D and 3D myotubes co-cultured with induced pluripotent stem cell-derived motor neurons. Reviewed

Kantaro Yoshioka, Akira Ito, Yoshinori Kawabe, Masamichi Kamihira

Journal of bioscience and bioengineering Vol. 129 ( 4 ) page： 486 - 493 2020.4

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

Motor neurons differentiated from induced pluripotent stem (iPS) cells have attracted attention for use in the construction of drug screening systems for neuronal diseases, such as amyotrophic lateral sclerosis. However, conventional drug screening systems using 2-dimensional (2D) cultures of iPS cell-derived motor neurons often evaluate the cell survival rate, morphological changes in the cells and/or gene expression analysis, and these parameters do not always reflect the actual functions of motor neurons, i.e., the induction of muscle contractions. In the present study, we developed a neuromuscular junction model comprising motor neurons and myotubes, which were differentiated from iPS cells and C2C12 myoblasts, respectively. Using this model, the contractile activity and force generation of the myotubes via the neuromuscular junction were successfully measured in both two- and three-dimensional (3D) cell culture systems. The results suggested that this neuromuscular junction model can be used to construct a drug candidate screening system for neuronal diseases.

DOI： 10.1016/j.jbiosc.2019.10.004

Web of Science

PubMed

Targeted knock-in into the OVA locus of chicken cells using CRISPR/Cas9 system with homology-independent targeted integration. Reviewed

Ming Shi, Yoshinori Kawabe, Akira Ito, Masamichi Kamihira

Journal of bioscience and bioengineering Vol. 129 ( 3 ) page： 363 - 370 2020.3

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

It is anticipated that transgenic avian species will be used as living bioreactors for the production of biopharmaceutical proteins. Precise tissue-specific expression of exogenous genes is a major challenge for the development of avian bioreactors. No robust vector is currently available for highly efficient and specific expression. In recent years, genome-editing techniques such as the CRISPR/Cas9 system have emerged as efficient and user-friendly genetic modification tools. Here, to apply the CRISPR/Cas9 system for the development of transgenic chickens, guide RNA sequences (gRNAs) of the CRISPR/Cas9 system for the ovalbumin (OVA) locus were evaluated for the oviduct-specific expression of exogenous genes. An EGFP gene expression cassette was introduced into the OVA locus of chicken DF-1 and embryonic fibroblasts using the CRISPR/Cas9 system mediated by homology-independent targeted integration. For the knock-in cells, EGFP expression was successfully induced by activation of the endogenous OVA promoter using the dCas9-VPR transactivation system. The combination of gRNAs designed around the OVA TATA box was important to induce endogenous OVA gene expression with high efficiency. These methods provide a useful tool for studies on the creation of transgenic chicken bioreactors and the activation of tissue-specific promoters.

DOI： 10.1016/j.jbiosc.2019.09.011

Web of Science

PubMed

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