Updated on 2022/06/06

写真a

 
SAKAI Kiyoshi
 
Organization
Nagoya University Hospital Oral and Maxillofacial Surgery Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor
External link

Degree 1

  1. 博士(医学) ( 2012.3   名古屋大学 ) 

Research Interests 4

  1. 組織発生

  2. Stem cells

  3. 細胞老化

  4. 組織再生

Research Areas 2

  1. Life Science / Regenerative dentistry and dental engineering

  2. Life Science / Surgical dentistry

Current Research Project and SDGs 1

  1. 頭頸部領域における再生医療開発

Research History 6

  1. Nagoya University   Oral and Maxillofacial Surgery, Hospital   Assistant Professor

    2021.7

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  2. Nagoya University   Graduate School of Medicine Program in Integrated Medicine Head and Neck and Sensory Organ Medicine   Assistant Professor

    2016.7 - 2021.6

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  3. Nagoya University   Oral and Maxillofacial Surgery, Hospital

    2015.10 - 2016.6

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  4. アメリカ国立衛生研究所 NIDCR Visiting Fellow

    2012.6 - 2015.9

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  5. Nagoya University   Graduate School of Medicine

    2012.4 - 2012.6

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  6. Nagoya University   Hospital

    2006.4 - 2008.3

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Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    - 2012.3

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    Country: Japan

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  2. Tsurumi University   Faculty of Dentistry

    - 2005.3

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    Country: Japan

Professional Memberships 8

  1. 日本口腔外科学会

  2. 日本口腔科学会

  3. 日本顎変形症学会

  4. 日本再生医療学会

  5. 歯科基礎医学会

  6. 日本口蓋裂学会

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  7. 日本口腔インプラント学会

  8. 日本顎関節学会

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Awards 2

  1. 歯科基礎医学会モリタ優秀発表賞

    2016.8   歯科基礎医学会   歯原性上皮細胞のエナメル芽細胞への分化におけるEpiprofinとT-box1の役割

    酒井陽, 吉崎恵悟, 千葉雄太, 池内友子, 山本朗仁, 日比英晴, 山田吉彦

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

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  2. 第11回日本再生医療学会総会 若手研究奨励賞

    2012.6   日本再生医療学会   脊髄損傷における歯髄幹細胞の多面的神経再生効果

    酒井陽

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    Country:Japan

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Papers 26

  1. Langerhans cell histiocytosis of single-system multifocal bone, including the mandible, in a 22-month-old child: A case report Reviewed

    Kiyoshi Sakai, Noriyuki Yamamoto, Satoshi Yamaguchi, Kazuto Okabe, Yoshiro Koma, Hideharu Hibi

    Oral Science International     2022.6

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: https://doi.org/10.1002/osi2.1147

  2. Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence Reviewed International coauthorship

    Dong Jiao, Sakai Kiyoshi, Koma Yoshiro, Watanabe Junna, Liu Kehong, Maruyama Hiroshi, Sakaguchi Kohei, Hibi Hideharu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 575   page: 28 - 35   2021.10

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2021.08.046

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  3. Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis. Reviewed

    Muto H, Ito T, Tanaka T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Maeda K, Honda T, Ishikawa T, Kato A, Ohshiro T, Kano F, Yamamoto A, Sakai K, Hibi H, Ishigami M, Fujishiro M

    Scientific reports   Vol. 11 ( 1 ) page: 18778   2021.9

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

    DOI: 10.1038/s41598-021-98254-8

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  4. Coexistence of Sjogren's syndrome and bilateral ranulas: A case report and review of the literature Reviewed

    Koma Yoshiro, Fujimoto Takehiro, Sakai Kiyoshi, Sugimura Yukiko, Yamaguchi Satoshi, Hibi Hideharu

    ORAL SCIENCE INTERNATIONAL     2021.9

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    Sjögren's syndrome and ranulas are relatively frequently occurring diseases. However, when they occur simultaneously, its clinical features and pathogenesis remain unclear. Here, we report a patient with bilateral ranulas. Magnetic resonance imaging at diagnosis revealed a “salt and pepper” appearance in bilateral parotid glands, leading a diagnosis of asymptomatic Sjögren's syndrome. She was successfully treated with excision of the left sublingual gland and sclerotherapy. A literature review suggests that this coexistence may not be very rare. In addition, it may be characterized by a high prevalence of bilateral ranulas.

    DOI: 10.1002/osi2.1121

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  5. Hyperparathyroidism-jaw tumor syndrome with bilateral ossifying fibromas in the mandible: A case report Reviewed International journal

    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology     2021.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology  

    DOI: 10.1016/j.ajoms.2021.01.005

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  6. Extracellular Vesicles of Stem Cells to Prevent BRONJ Reviewed

    Watanabe J, Sakai K, Urata Y, Toyama N, Nakamichi E, Hibi H

    Journal of Dental Research   Vol. 99 ( 5 ) page: 552 - 560   2020.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1177/0022034520906793

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  7. 先天性無フィブリノゲン血症患者の抜歯術における周術期管理を行った1例 Reviewed

    岡部 一登, 土屋 周平, 酒井 陽, 松下 義泰, 杉本 圭佑, 日比 英晴

    日本口腔外科学会雑誌   Vol. 65 ( 8 ) page: 507 - 512   2019.8

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(公社)日本口腔外科学会  

    13歳男子。右下6番根尖性歯周炎に起因した下顎骨骨膜下膿瘍および頬部蜂窩織炎と診断した。先天性無フィブリノゲン(Fbg)血症のため消炎処置前にFbg製剤2gを投与し、歯肉の腫脹部より膿瘍切開術を施行した。同日よりアモキシシリン投与を開始し、翌日より切開部からの洗浄を継続し、7日後には顎下部や口腔内の腫脹は消退した。翌月に右下6番を抜歯し、抜歯後は事前に製作した創部保護床を終日装着させた。Fbg製剤は血中Fbg濃度100mg/dL以上を目標に抜歯当日3g、抜歯後1日目に2g、抜歯後2日目に2g投与した。抜歯後2日目には抜歯窩の縫合糸は脱落していたが幼若な血餅で満たされ、引き続き創部保護床は終日装着したままとして退院した。抜歯後8日目に創部保護床を除去し、処置後の異常出血はなく、治癒の遅延も認めなかった。

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  8. Identification of the Novel Tooth-Specific Transcription Factor AmeloD Reviewed International coauthorship

    He B, Chiba Y, Li H, de Vega S, Tanaka K, Yoshizaki K, Ishijima M, Yuasa K, Ishikawa M, Rhodes C, Sakai K, Zhang P, Fukumoto S, Zhou X, Yamada Y

    Journal of Dental Research   Vol. 98 ( 2 ) page: 234 - 241   2019.2

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    DOI: 10.1177/0022034518808254

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  9. Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia. Reviewed International journal

    Takeshi Tsuruta, Kiyoshi Sakai, Junna Watanabe, Wataru Katagiri, Hideharu Hibi

    PLOS ONE   Vol. 13 ( 12 ) page: e0208938   2018.12

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.

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  10. 他家骨髄由来間葉系細胞の移植による骨再生の検討

    渡邊 純奈, 片桐 渉, 大杉 将嗣, 酒井 陽, 岡部 一登, 椙村 有紀子, 坂口 晃平, 鶴田 剛士, 日比 英晴

    日本口腔インプラント学会誌   Vol. 31 ( 2 ) page: E75 - E75   2018.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(公社)日本口腔インプラント学会  

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  11. Mediator 1 Contributes to Enamel Mineralization as a Coactivator for Notch1 Signaling and Stimulates Transcription of the Alkaline Phosphatase Gene Reviewed International coauthorship

    Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Masaki Ishikawa, Ichiro Takahashi, Satoshi Fukumoto, Pamela Den Besten, Daniel D. Bikle, Yuko Oda, Yoshihiko Yamada

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 292 ( 33 ) page: 13531-13540   2017.8

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    DOI: 10.1074/jbc.M117.780866

  12. ラット末梢性嚥下障害モデルを用いた乳歯歯髄幹細胞由来成長因子の治療効果の検討 International journal

    鶴田 剛士, 片桐 渉, 大杉 将嗣, 酒井 陽, 若山 有紀子, 坂口 晃平, 渡邊 純奈, 日比 英晴

    日本口腔科学会雑誌   Vol. 66 ( 2 ) page: 207 - 208   2017.7

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(NPO)日本口腔科学会  

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  13. Pannexin 3 and connexin 43 modulate skeletal development through their distinct functions and expression patterns Reviewed International coauthorship International journal

    Masaki Ishikawa, Geneva L. Williams, Tomoko Ikeuchi, Kiyoshi Sakai, Satoshi Fukumoto, Yoshihiko Yamada

    JOURNAL OF CELL SCIENCE   Vol. 129 ( 5 ) page: 1018 - 1030   2016.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:COMPANY OF BIOLOGISTS LTD  

    Pannexin 3 (Panx3) and connexin 43 (Cx43; also known as GJA1) are two major gap junction proteins expressed in osteoblasts. Here, we studied their functional relationships in skeletal formation by generating Panx3(-/-) and Panx3(-/-); Cx43(-/-) mice and comparing their skeletal phenotypes with Cx43(-/-) mice. Panx3(-/-) mice displayed defects in endochondral and intramembranous ossification, resulting in severe dwarfism and reduced bone density. The skeletal abnormalities of Panx3(-/-); Cx43(-/-) mice were similar to those in Panx3(-/-) mice. The gross appearance of newborn Cx43(-/-) skeletons showed no obvious abnormalities, except for less mineralization of the skull. In Panx3(-/-) mice, proliferation of chondrocytes and osteoblasts increased and differentiation of these cells was inhibited. Panx3 promoted expression of osteogenic proteins such as ALP and Ocn (also known as ALPL and BGLAP, respectively), as well as Cx43, by regulating Osx (also known as SP7) expression. Panx3 was induced in the early differentiation stage and reduced during the maturation stage of osteoblasts, when Cx43 expression increased in order to promote mineralization. Furthermore, only Panx3 functioned as an endoplasmic reticulum (ER) Ca2+ channel to promote differentiation, and it could rescue mineralization defects in Cx43(-/-) calvarial cells. Our findings reveal that Panx3 and Cx43 have distinct functions in skeletal formation.

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  14. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats Reviewed International journal

    Hiromi Fujii, Kohki Matsubara, Kiyoshi Sakai, Mikako Ito, Kinji Ohno, Minoru Ueda, Akihito Yamamoto

    BRAIN RESEARCH   Vol. 1613   page: 59 - 72   2015.7

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    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDS), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parldnsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD. (C) 2015 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2015.04.001

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  15. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity Reviewed International journal

    Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto

    JOURNAL OF NEUROSCIENCE   Vol. 35 ( 6 ) page: 2452 - 2464   2015.2

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    Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.

    DOI: 10.1523/JNEUROSCI.4088-14.2015

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  16. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation Reviewed International journal

    Takashi Nakamura, Yasuo Yoshitomi, Kiyoshi Sakai, Vyomesh Patel, Satoshi Fukumoto, Yoshihiko Yamada

    JOURNAL OF CELL SCIENCE   Vol. 127 ( 24 ) page: 5261 - 5272   2014.12

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    The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development.

    DOI: 10.1242/jcs.156778

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  17. Ablation of Coactivator Med1 Switches the Cell Fate of Dental Epithelia to That Generating Hair Reviewed International coauthorship International journal

    Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Bing He, Chak Fong, Yoshihiko Yamada, Daniel D. Bikle, Yuko Oda

    PLOS ONE   Vol. 9 ( 6 )   2014.6

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    Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.

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  18. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury Reviewed International journal

    Akihito Yamamoto, Kiyoshi Sakai, Kohki Matsubara, Fumiya Kano, Minoru Ueda

    NEUROSCIENCE RESEARCH   Vol. 78   page: 16 - 20   2014.1

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    Spinal cord injury (SCI) often leads to persistent functional deficits due to the loss of neurons and glia and to limited axonal regeneration after such injury. Recently, three independent groups have reported marked recovery of hindlimb locomotor function after the transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) into rats or mice with acute, sub-acute or chronic SCI. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for treating SCI. Experimental data from multiple preclinical studies suggest that pulp stem cells may promote functional recovery after SCI through multifaceted neuro-regenerative activities. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2013.10.010

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  19. Analysis of the neuroregenerative activities of mesenchymal stem cells in functional recovery after rat spinal cord injury Reviewed International journal

    A. Yamamoto, K. Matsubara, F. Kano, K. Sakai

    Methods in Molecular Biology     page: 321-328   2014

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  20. Multifaceted Neuro-Regenerative Activities of Human Dental Pulp Stem Cells for Functional Recovery after Spinal Cord Injury International journal

    Yamamoto Akihito, Matsubara Kohki, Sakai Kiyoshi, Kano Fumiya, Ueda Minoru

    NEW TRENDS IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE - OFFICIAL BOOK OF THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE     page: 67 - 79   2014

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    DOI: 10.5772/58906

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  21. Analysis of the Neuroregenerative Activities of Mesenchymal Stem Cells in Functional Recovery after Rat Spinal Cord Injury International journal

    Yamamoto Akihito, Matsubara Kohki, Kano Fumiya, Sakai Kiyoshi

    ANIMAL MODELS FOR STEM CELL THERAPY   Vol. 1213   page: 321 - 328   2014

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    DOI: 10.1007/978-1-4939-1453-1_26

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  22. Human Dental Pulp-Derived Stem Cells Protect Against Hypoxic-Ischemic Brain Injury in Neonatal Mice Reviewed International journal

    Mari Yamagata, Akihito Yamamoto, Eisuke Kako, Naoko Kaneko, Kohki Matsubara, Kiyoshi Sakai, Kazunobu Sawamoto, Minoru Ueda

    STROKE   Vol. 44 ( 2 ) page: 551 - 554   2013.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Background and Purpose-Perinatal hypoxia-ischemia (HI) has high rates of neurological deficits and mortality. So far, no effective treatment for HI brain injury has been developed. In this study, we investigated the therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) for the treatment of neonatal HI brain injury.
    Methods-Unilateral HI was induced in postnatal day 5 (P5) mice. Twenty-four hours later, SHED, human skin fibroblasts, or serum-free conditioned medium derived from these cells was injected into the injured brain. The effects of cell transplantation or conditioned medium injection on the animals' neurological and pathophysiological recovery were evaluated.
    Results-Transplanted SHED, but not fibroblasts, significantly reduced the HI-induced brain-tissue loss and improved neurological function. SHED also improved the survival of the HI mice. The engrafted SHED rarely differentiated into neural lineages; however, their transplantation inhibited the expression of proinflammatory cytokines, increased the expression of anti-inflammatory ones, and significantly reduced apoptosis. Notably, the intracerebral administration of SHED-conditioned medium also significantly improved the neurological outcome, inhibited apoptosis, and reduced tissue loss.
    Conclusions-SHED transplantation into the HI-injured brain resulted in remarkable neurological and pathophysiological recovery. Our findings indicate that paracrine factors derived from SHED support a neuroprotective microenvironment in the HI brain. SHED graft and SHED-conditioned medium may provide a novel neuroprotective therapy for HI. (Stroke. 2013;44:551-554.)

    DOI: 10.1161/STROKEAHA.112.676759

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  23. Human umbilical cord-derived mesenchymal stromal cells promote sensory recovery in a spinl cord injury rat model Reviewed International journal

    S. Takikawa, A. Yamamoto, K. Sakai, R. Shohara, A. Iwase, F. Kikkawa, M. Ueda

    Stem Cell Discovery     page: 155-163   2013

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  24. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms Reviewed International journal

    Kiyoshi Sakai, Akihito Yamamoto, Kohki Matsubara, Shoko Nakamura, Mami Naruse, Mari Yamagata, Kazuma Sakamoto, Ryoji Tauchi, Norimitsu Wakao, Shiro Imagama, Hideharu Hibi, Kenji Kadomatsu, Naoki Ishiguro, Minoru Ueda

    JOURNAL OF CLINICAL INVESTIGATION   Vol. 122 ( 1 ) page: 80 - 90   2012.1

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER SOC CLINICAL INVESTIGATION INC  

    Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

    DOI: 10.1172/JCI59251

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  25. Stability of a Locking Plate and Self-Drilling Screws as Orthodontic Skeletal Anchorage in the Maxilla: A Retrospective Study Reviewed International journal

    Hidebaru Hibi, Kiyoshi Sakai, Tomoo Oda, Hisashi Hattori, Minoru Ueda, Masaru Sakai

    JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   Vol. 68 ( 8 ) page: 1783 - 1787   2010.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:W B SAUNDERS CO-ELSEVIER INC  

    Purpose: The aim of this retrospective study was to determine the success rate of an orthodontic skeletal anchorage system consisting of a locking plate and 2 self-drilling screws to intrude the upper molars and detect factors that contribute to its stability.
    Patients and Methods: The subjects were 32 orthodontic and generally healthy patients who had skeletal anchorage plates placed supraperiosteally and unilaterally or bilaterally. The anchorage plate was considered successful if the plate remained stable throughout the period of intrusion of the upper molar without any movement, persistent pain, or infection and was then retrieved without difficulty. The success rates of the anchorage plate were statistically analyzed on the basis of clinically categorized variables.
    Results: The 32 patients comprised 6 male and 26 female individuals with ages ranging from 11.4 to 35.1 years. The overall success rate of the total 61 plates was 93.4%. No significant differences were observed among the respective success rates analyzed in accordance with gender, age, side of placement, and length of the screws. The thickness of the bony walls that supported the screws was significantly greater in the success group (mean 1.6 +/- SD, 0.2 vs 1.0 +/- 0.1 mm, P < .001).
    Conclusion: Bone thickness is a critical factor in supporting the self-drilling screws and locking plate. Skeletal anchorage combining the plate and 2 screws promises a higher success rate with a thicker bone than with the threshold value of thickness that exists within the 1.1 to 1 4 mm range in the maxillary walls. 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1783-1787, 2010

    DOI: 10.1016/j.joms.2009.09.020

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  26. 多発性骨髄腫に対するビスフォスフォネート投与に関連したと考えられる上顎骨壊死の1例 International journal

    酒井 陽, 片桐 渉, 服部 宇, 金山 健夫, 上田 実, 山田 陽一, 日比 英晴, 伊藤 憲治

    日本口腔科学会雑誌   Vol. 57 ( 3 ) page: 334 - 334   2008.7

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Books 6

  1. Peripheral Nerve Regeneration in a Novel Rat Model of Dysphagia. Reviewed International journal

    Sakai K, Tsuruta T, Watanabe J, Sugimura Y, Sakaguchi K, Katagiri W, Hibi H( Role: Contributor)

    Methods in molecular biology (Clifton, N.J.)  2020.5 

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  2. New Trend in Tissue Engineering and Regenerative Medicine Official Book of the Japanese Society Regenerative Medicine

    A. Yamamoto, K. Matsubara, K. Sakai, F. Kano, and, M. Ueda( Role: Joint author)

    INTECH  2014 

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  3. Orthodontic anchorage using a locking plate and self-drilling miniscrew implants for the posterior maxilla

    Hibi H, Sakai K, Ueda M, Sakai M( Role: Joint author)

    Mosby Elsevier  2014 

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  4. ヒト脱落乳歯・智歯の歯髄幹細胞による新しい脊髄損傷治療の可能性

    酒井陽, 山本朗仁, 上田実( Role: Joint author)

    クインテッセンス出版  2013 

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  5. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms

    酒井 陽( Role: Joint author)

    [s.n.]  2012 

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    CiNii Books

  6. 歯髄幹細胞を用いた脊髄損傷の再生医療 医学のあゆみ

    山本朗仁, 酒井陽( Role: Joint author)

    医歯薬出版株式会社  2011 

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MISC 27

  1. 異なるプレートを用いたLe Fort I型骨切り術後の骨片の安定性に関する検討 International journal

    佐世 暁, 藤尾 正人, 荻須 宏太, 坪井 亮仁, 酒井 陽, 日比 英晴

    日本顎変形症学会雑誌   Vol. 30 ( 2 ) page: 167 - 167   2020.5

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  2. 低血圧麻酔下の顎矯正手術中に心停止をきたした顎変形症の一例 International journal

    坂口 晃平, 藤尾 正人, 酒井 陽, 日比 英晴

    日本顎変形症学会雑誌   Vol. 30 ( 2 ) page: 172 - 172   2020.5

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  3. 下顎広範囲に進展した紡錘細胞癌の1例 International journal

    丸山 裕, 山本 憲幸, 山口 聡, 坂倉 寛紀, 西川 雅也, 酒井 陽, 日比 英晴

    日本口腔科学会雑誌   Vol. 68 ( 2 ) page: 115 - 115   2019.7

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  4. BRONJ発症におけるエクソソームの効果の検討 International journal

    渡邊 純奈, 酒井 陽, 日比 英晴

    Journal of Oral Biosciences Supplement   Vol. 2018   page: 248 - 248   2018.9

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  5. ビスホスホネート関連顎骨壊死に対する間葉系幹細胞由来エクソソームを用いた治療の可能性 International journal

    渡邊 純奈, 酒井 陽, 岡部 一登, 若山 有紀子, 坂口 晃平, 鶴田 剛士, 日比 英晴

    日本口腔科学会雑誌   Vol. 67 ( 2 ) page: 162 - 162   2018.7

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  6. 下顎臼歯部に発生した巨細胞修復性肉芽腫の1例 International journal

    酒井 陽, 片桐 渉, 大杉 将嗣, 田原春 早織, 日比 英晴

    日本口腔科学会雑誌   Vol. 67 ( 1 ) page: 48 - 49   2018.3

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  7. 組織再生に関わる基礎研究基盤の現状 エピプロフィンは歯原性上皮細胞のエナメル芽細胞系への誘導と分化を制御する多機能制御因子である International journal

    山田 吉彦, 酒井 陽, 千葉 雄太, Mahboubi Darius, 池内 友子, 石河 真幸, 中村 卓史, 福本 敏

    Journal of Oral Biosciences Supplement   Vol. 2016   page: 57 - 58   2016.9

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  8. 歯原性上皮細胞のエナメル芽細胞への分化におけるEpiprofinとT-box1の役割 International journal

    酒井 陽, 吉崎 恵悟, 千葉 雄太, 池内 友子, 山本 朗仁, 日比 英晴, 山田 吉彦

    Journal of Oral Biosciences Supplement   Vol. 2016   page: 357 - 357   2016.9

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  9. Pannexin 3 and connexin 43 modulate skeletal development through their distinct functions and expression patterns Reviewed International journal

    Masaki Ishikawa, Geneva L. Williams, Tomoko Ikeuchi, Kiyoshi Sakai, Satoshi Fukumoto, Yoshihiko Yamada

    JOURNAL OF CELL SCIENCE   Vol. 129 ( 5 ) page: 1018 - 1030   2016.3

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    Pannexin 3 (Panx3) and connexin 43 (Cx43; also known as GJA1) are two major gap junction proteins expressed in osteoblasts. Here, we studied their functional relationships in skeletal formation by generating Panx3(-/-) and Panx3(-/-); Cx43(-/-) mice and comparing their skeletal phenotypes with Cx43(-/-) mice. Panx3(-/-) mice displayed defects in endochondral and intramembranous ossification, resulting in severe dwarfism and reduced bone density. The skeletal abnormalities of Panx3(-/-); Cx43(-/-) mice were similar to those in Panx3(-/-) mice. The gross appearance of newborn Cx43(-/-) skeletons showed no obvious abnormalities, except for less mineralization of the skull. In Panx3(-/-) mice, proliferation of chondrocytes and osteoblasts increased and differentiation of these cells was inhibited. Panx3 promoted expression of osteogenic proteins such as ALP and Ocn (also known as ALPL and BGLAP, respectively), as well as Cx43, by regulating Osx (also known as SP7) expression. Panx3 was induced in the early differentiation stage and reduced during the maturation stage of osteoblasts, when Cx43 expression increased in order to promote mineralization. Furthermore, only Panx3 functioned as an endoplasmic reticulum (ER) Ca2+ channel to promote differentiation, and it could rescue mineralization defects in Cx43(-/-) calvarial cells. Our findings reveal that Panx3 and Cx43 have distinct functions in skeletal formation.

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  10. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats Reviewed International journal

    Hiromi Fujii, Kohki Matsubara, Kiyoshi Sakai, Mikako Ito, Kinji Ohno, Minoru Ueda, Akihito Yamamoto

    BRAIN RESEARCH   Vol. 1613   page: 59 - 72   2015.7

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    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDS), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parldnsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD. (C) 2015 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2015.04.001

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  11. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity Reviewed International journal

    Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto

    JOURNAL OF NEUROSCIENCE   Vol. 35 ( 6 ) page: 2452 - 2464   2015.2

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    Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.

    DOI: 10.1523/JNEUROSCI.4088-14.2015

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  12. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation Reviewed International journal

    Takashi Nakamura, Yasuo Yoshitomi, Kiyoshi Sakai, Vyomesh Patel, Satoshi Fukumoto, Yoshihiko Yamada

    JOURNAL OF CELL SCIENCE   Vol. 127 ( 24 ) page: 5261 - 5272   2014.12

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    The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development.

    DOI: 10.1242/jcs.156778

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  13. Ablation of Coactivator Med1 Switches the Cell Fate of Dental Epithelia to That Generating Hair Reviewed International journal

    Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Bing He, Chak Fong, Yoshihiko Yamada, Daniel D. Bikle, Yuko Oda

    PLOS ONE   Vol. 9 ( 6 )   2014.6

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    Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.

    DOI: 10.1371/journal.pone.0099991

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  14. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury Reviewed International journal

    Akihito Yamamoto, Kiyoshi Sakai, Kohki Matsubara, Fumiya Kano, Minoru Ueda

    NEUROSCIENCE RESEARCH   Vol. 78   page: 16 - 20   2014.1

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    Spinal cord injury (SCI) often leads to persistent functional deficits due to the loss of neurons and glia and to limited axonal regeneration after such injury. Recently, three independent groups have reported marked recovery of hindlimb locomotor function after the transplantation of human adult dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) into rats or mice with acute, sub-acute or chronic SCI. This review summarizes the primary characteristics of human dental pulp stem cells and their therapeutic benefits for treating SCI. Experimental data from multiple preclinical studies suggest that pulp stem cells may promote functional recovery after SCI through multifaceted neuro-regenerative activities. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2013.10.010

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  15. Analysis of the neuroregenerative activities of mesenchymal stem cells in functional recovery after rat spinal cord injury Reviewed International journal

    A. Yamamoto, K. Matsubara, F. Kano, K. Sakai

    Methods in Molecular Biology     page: 321-328   2014

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  16. Human Dental Pulp-Derived Stem Cells Protect Against Hypoxic-Ischemic Brain Injury in Neonatal Mice Reviewed International journal

    Mari Yamagata, Akihito Yamamoto, Eisuke Kako, Naoko Kaneko, Kohki Matsubara, Kiyoshi Sakai, Kazunobu Sawamoto, Minoru Ueda

    STROKE   Vol. 44 ( 2 ) page: 551 - 554   2013.2

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    Background and Purpose-Perinatal hypoxia-ischemia (HI) has high rates of neurological deficits and mortality. So far, no effective treatment for HI brain injury has been developed. In this study, we investigated the therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) for the treatment of neonatal HI brain injury.
    Methods-Unilateral HI was induced in postnatal day 5 (P5) mice. Twenty-four hours later, SHED, human skin fibroblasts, or serum-free conditioned medium derived from these cells was injected into the injured brain. The effects of cell transplantation or conditioned medium injection on the animals' neurological and pathophysiological recovery were evaluated.
    Results-Transplanted SHED, but not fibroblasts, significantly reduced the HI-induced brain-tissue loss and improved neurological function. SHED also improved the survival of the HI mice. The engrafted SHED rarely differentiated into neural lineages; however, their transplantation inhibited the expression of proinflammatory cytokines, increased the expression of anti-inflammatory ones, and significantly reduced apoptosis. Notably, the intracerebral administration of SHED-conditioned medium also significantly improved the neurological outcome, inhibited apoptosis, and reduced tissue loss.
    Conclusions-SHED transplantation into the HI-injured brain resulted in remarkable neurological and pathophysiological recovery. Our findings indicate that paracrine factors derived from SHED support a neuroprotective microenvironment in the HI brain. SHED graft and SHED-conditioned medium may provide a novel neuroprotective therapy for HI. (Stroke. 2013;44:551-554.)

    DOI: 10.1161/STROKEAHA.112.676759

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  17. Human umbilical cord-derived mesenchymal stromal cells promote sensory recovery in a spinl cord injury rat model Reviewed International journal

    S. Takikawa, A. Yamamoto, K. Sakai, R. Shohara, A. Iwase, F. Kikkawa, M. Ueda

    Stem Cell Discovery     page: 155-163   2013

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  18. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms Reviewed International journal

    Kiyoshi Sakai, Akihito Yamamoto, Kohki Matsubara, Shoko Nakamura, Mami Naruse, Mari Yamagata, Kazuma Sakamoto, Ryoji Tauchi, Norimitsu Wakao, Shiro Imagama, Hideharu Hibi, Kenji Kadomatsu, Naoki Ishiguro, Minoru Ueda

    JOURNAL OF CLINICAL INVESTIGATION   Vol. 122 ( 1 ) page: 80 - 90   2012.1

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    Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

    DOI: 10.1172/JCI59251

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  19. 骨延長部の骨形成過程におけるSDF-1/CXCR4システムの役割 International journal

    藤尾 正人, 山本 朗仁, 日比 英晴, 木下 一彦, 匠原 龍太郎, 酒井 陽, 山形 まり, 上田 実

    Journal of Oral Biosciences   Vol. 52 ( Suppl ) page: 103 - 103   2010.9

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  20. ラット脊髄完全切断モデルにおけるヒト歯髄細胞移植効果の検討 International journal

    酒井 陽, 山本 朗仁, 日比 英晴, 山田 陽一, 藤尾 正人, 山形 まり, 今釜 史郎, 若尾 典充, 田内 亮吏, 上田 実

    Journal of Oral Biosciences   Vol. 52 ( Suppl ) page: 91 - 91   2010.9

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  21. ヒト臍帯由来の組織再生細胞を用いた骨再生療法の開発 International journal

    匠原 龍太郎, 山本 朗仁, 日比 英晴, 藤尾 正人, 酒井 陽, 山形 まり, 上田 実

    Journal of Oral Biosciences   Vol. 52 ( Suppl ) page: 117 - 117   2010.9

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  22. Stability of a Locking Plate and Self-Drilling Screws as Orthodontic Skeletal Anchorage in the Maxilla: A Retrospective Study Reviewed International journal

    Hidebaru Hibi, Kiyoshi Sakai, Tomoo Oda, Hisashi Hattori, Minoru Ueda, Masaru Sakai

    JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY   Vol. 68 ( 8 ) page: 1783 - 1787   2010.8

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    Purpose: The aim of this retrospective study was to determine the success rate of an orthodontic skeletal anchorage system consisting of a locking plate and 2 self-drilling screws to intrude the upper molars and detect factors that contribute to its stability.
    Patients and Methods: The subjects were 32 orthodontic and generally healthy patients who had skeletal anchorage plates placed supraperiosteally and unilaterally or bilaterally. The anchorage plate was considered successful if the plate remained stable throughout the period of intrusion of the upper molar without any movement, persistent pain, or infection and was then retrieved without difficulty. The success rates of the anchorage plate were statistically analyzed on the basis of clinically categorized variables.
    Results: The 32 patients comprised 6 male and 26 female individuals with ages ranging from 11.4 to 35.1 years. The overall success rate of the total 61 plates was 93.4%. No significant differences were observed among the respective success rates analyzed in accordance with gender, age, side of placement, and length of the screws. The thickness of the bony walls that supported the screws was significantly greater in the success group (mean 1.6 +/- SD, 0.2 vs 1.0 +/- 0.1 mm, P < .001).
    Conclusion: Bone thickness is a critical factor in supporting the self-drilling screws and locking plate. Skeletal anchorage combining the plate and 2 screws promises a higher success rate with a thicker bone than with the threshold value of thickness that exists within the 1.1 to 1 4 mm range in the maxillary walls. 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1783-1787, 2010

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  23. 組織幹細胞による難治性疾患治療の現状と未来 脱落乳歯および智歯由来の歯髄幹細胞による神経再生治療 International journal

    酒井 陽, 山本 朗仁, 日比 英晴, 山田 陽一, 今釜 史郎, 若尾 典充, 田内 亮吏, 上田 実

    Inflammation and Regeneration   Vol. 30 ( 4 ) page: 314 - 314   2010.7

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    Language:Japanese   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:(一社)日本炎症・再生医学会  

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  24. ヒト臍帯由来の組織再生細胞を用いた骨再生療法の開発 International journal

    匠原 龍太郎, 滝川 幸子, 山本 朗仁, 日比 英晴, 藤尾 正人, 酒井 陽, 山形 まり, 後藤 真紀, 岩瀬 明, 吉川 史隆, 上田 実

    Inflammation and Regeneration   Vol. 30 ( 4 ) page: 362 - 362   2010.7

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    Language:Japanese   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:(一社)日本炎症・再生医学会  

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  25. 骨延長部の骨形成過程におけるSDF-1/CXCR4システムの役割 International journal

    藤尾 正人, 山本 朗仁, 日比 英晴, 金子 正, 木下 一彦, 匠原 龍太郎, 酒井 陽, 山形 まり, 上田 実

    Inflammation and Regeneration   Vol. 30 ( 4 ) page: 364 - 364   2010.7

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  26. ロッキングプレートによる矯正用アンカーの臨床統計的検討 International journal

    酒井 陽, 日比 英晴, 小田 知生, 服部 宇, 上田 実

    日本顎変形症学会雑誌   Vol. 19 ( 2 ) page: 73 - 73   2009.5

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  27. 多発性骨髄腫に対するビスフォスフォネート投与に関連したと考えられる上顎骨壊死の1例 Reviewed International journal

    酒井 陽, 片桐 渉, 服部 宇, 金山 健夫, 上田 実, 山田 陽一, 日比 英晴, 伊藤 憲治

    日本口腔科学会雑誌   Vol. 57 ( 3 ) page: 334 - 334   2008.7

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▼display all

Presentations 56

  1. 有限要素解析法を用いたLe Fort I型骨切り術の固定法

    佐世暁,藤尾正人,坪井亮仁,酒井陽,奥村大,日比英晴

    第66回日本口腔外科学会  2021.11.12 

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:幕張メッセ   Country:Japan  

  2. 両側ラヌーラを契機として診断されたシェーグレン症候群の1例

    小間義朗,藤本雄大,酒井陽,山口聡,日比英晴

    第66回日本口腔外科学会  2020.11.12 

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    Event date: 2021.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:幕張メッセ   Country:Japan  

  3. Comparison of biomechanical analysis after Le Fort I osteotomy with two square-shaped and four L-shaped titanium plates using 3D-FEA International conference

    Sayo A, Fujio M, Tsuboi M, Sakai K, Okumura D, Hibi H

    60th Congress of the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons  2021.11.4 

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    Event date: 2021.11

    Language:English   Presentation type:Poster presentation  

    Venue:webinar   Country:Korea, Republic of  

  4. Exosomes derived from mesenchymal stem cells stimulated by hypoxia accelerated osteogenesis International coauthorship International conference

    Sakaguchi K, Sakai K, Sugimura-Wakayama Y, Koma Y, Watanabe J, Maruyama H, Kehong L, Jial D, Hibi H

    2021 IADR/AADR/CADR General Session  

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    Event date: 2021.7

    Language:English   Presentation type:Poster presentation  

    Venue:アメリカ合衆国  

  5. 異なるプレートを用いたLe Fort I骨切り術後の生態力学的解析

    佐世暁,藤尾正人,坪井亮仁,酒井陽,奥村大,日比英晴

    第31回日本顎変形症学会   2021.6  web

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    Event date: 2021.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  6. シェーグレン症候群の唾液腺細胞老化に幹細胞由来細胞外小胞が与える影響

    小間義朗,酒井陽,渡邊純奈,椙村有紀子,坂口晃平,丸山裕,日比英晴

    第75回日本口腔科学会  2021.5.13 

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    Event date: 2021.5

    Language:Japanese   Presentation type:Poster presentation  

    Venue:ウェビナー   Country:Japan  

  7. ヒト歯髄幹細胞の無血清培養上清が皮弁の生着に与える効果の検討

    王芸霖,山口聡,陳暉,渡邊純奈,酒井陽,日比英晴

    第20回日本再生医療学会  2021.3.11 

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    Event date: 2021.3

    Language:English   Presentation type:Poster presentation  

    Venue:ウェビナー   Country:Japan  

  8. Human Dental Pulp Stem Cell-Derived Extracellular Vesicles Prevent the Functional Damage to Salivary Gland Caused by Irradiation

    Jiao Dong, Kiyoshi Sakai, Yoshiro Koma, Kehong Liu, Hiroshi Maruyama, Junna Watanabe, Hideharu Hibi

    The 2nd CIBoG Retreat 

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    Event date: 2021.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  9. Effects of hDPSCs-derived exosomes in novel salivary gland disease model International conference

    Koma Y, Sakai K, Jiao D, Watanabe J, Hibi H

    2020 IADR/AADR/CADR General Session 

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    Event date: 2020

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  10. 汎発性帯状疱疹を併発した不完全型Ramsay-Hunt症候群の1例

    宮坂紗季,岡部一登,酒井陽,若山有紀子,大森正裕,坂口晃平,日比英晴

    第63回日本口腔科学会中部地方部会 

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    Event date: 2020

    Language:Japanese  

    Country:Japan  

  11. 異なるプレートを用いたLe Fort I 型骨切り術後の骨片の安定性に関する検討

    佐世暁,藤尾正人,荻須宏太,坪井亮仁,酒井陽,日比英晴

    第30回日本顎変形症学会 

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    Event date: 2020

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  12. 低血圧麻酔下の顎矯正手術中に心停止をきたした顎変形症の一例

    坂口晃平,藤尾正人,酒井陽,日比英晴

    第30回日本顎変形症学会 

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    Event date: 2020

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  13. 唾液腺機能障害におけるヒト歯髄幹細胞由来細胞外小胞による予防効果の検討

    董嬌,酒井陽,小間義朗,渡邊純奈,日比英晴

    第62回歯科基礎医学会学術大会 

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    Event date: 2020

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  14. マウス唾液腺原基・脾細胞共培養系を用いた ex vivo シェーグレン症候群モデルにおけるヒト歯髄幹細胞由来細胞外小胞の効果

    小間義朗,酒井陽,Dong Jiao,丸山裕,Liu Kehong,渡邊純奈,日比英晴

    第62回歯科基礎医学会学術大会 

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    Event date: 2020

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  15. 骨造成後の骨補填材に感染が波及した1例

    渡邊純奈,岡部一登,酒井陽,藤尾正人,椙村有紀子,坂口晃平,佐世曉,日比英晴

    第50回日本口腔インプラント学会  

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    Event date: 2020

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  16. 骨再生についてのわれわれの取り組みの変遷

    岡部一登,藤尾正人,酒井陽,椙村有紀子,坂口晃平,渡邊純奈,日比英晴

    第50回日本口腔インプラント学会  

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    Event date: 2020

    Language:Japanese  

    Country:Japan  

  17. Le Fort I型骨切り術の固定法と術後の骨片変位量の検討

    藤尾正人,佐世暁,荻須宏太,土屋周平,酒井陽,日比英晴

    第64回日本口腔外科学会 

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    Event date: 2019

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  18. 転写因子Epfn-Tbx1 複合体を用いた歯原性上皮幹細胞分化制御の解明

    酒井陽,山本朗仁,日比英晴

    第64回日本口腔外科学会 

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    Event date: 2019

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  19. 下顎広範囲に進展した紡錘細胞癌の1例

    丸山裕,山本憲幸,山口聡,坂倉寛紀,西川雅也,酒井陽,日比英晴

    第73回日本口腔科学会 

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    Event date: 2019

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  20. デクスメデトミジンを使用した智歯抜歯術中の低酸素血症の予防:無作為比較対象研究

    田原春早織,坂口晃平,藤尾正人,酒井陽,西川雅也,山本憲幸,日比英晴,佐藤(朴)會士

    第64回日本口腔外科学会 

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    Event date: 2019

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  21. Bone regeneration using exosomes derived from hMSCs stimulated by hypoxia International conference

    Sakaguchi K, Sakai K, Sugimura Y, Watanabe J, Hibi H

    28th Annual Scientific Meeting EAO Congress 2019   2019 

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    Event date: 2019

    Language:English   Presentation type:Poster presentation  

    Country:Portugal  

  22. 歯髄幹細胞の脊髄損傷における多面的治療効果 Invited

    酒井陽

    第22回日本顎顔面インプラント学会 

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    Event date: 2018.12

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

    Venue:東京   Country:Japan  

  23. 間葉系幹細胞由来エクソソームを用いた BRONJに対する治療の有効性の検討

    渡邊純奈,酒井陽,岡部一登,椙村有紀子,坂口晃平,鶴田剛士,中道瑛司,日比英晴

    第63回日本口腔外科学会 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  24. Le Fort I 型骨切り術の固定法と術後安定性の検討

    藤尾正人,佐世暁,荻須宏太,土屋周平,酒井陽,日比英晴

    第63回日本口腔外科学会 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  25. 骨髄間葉系幹細胞が分泌するエクソソームによる新規骨再生法

    坂口晃平,酒井陽,椙村有紀子,鶴田剛士,渡邊純奈,片桐渉,日比英晴

    第63回日本口腔外科学会 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  26. 基礎研究をする口腔外科医 〜研究との出会いから現在まで〜

    酒井陽

    第63回日本口腔外科学会 第1回 若手口腔外科医交流会 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  27. BRONJ 発症におけるエクソソームの効果の検討

    渡邊純奈,酒井陽,日比英晴

    第60回歯科基礎医学会 

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    Event date: 2018.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:福岡   Country:Japan  

  28. A Novel Approach to Peripheral Nerve Regeneration Using Conditioned Media International conference

    Yukiko Sugimura, Kiyoshi Sakai, Hirotaka Wakayama, Kohei Sakaguchi, Takeshi Tsuruta, Junna Watanabe, Wataru Katagiri, Hideharu Hibi

    96th General Session & Exhibition of the IADR 

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    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Venue:London   Country:United Kingdom  

  29. Effects of mesenchymal stem cell-derived exosomes for rat BRONJ model International conference

    Watanabe J, Sakai K, Okabe K, Sugimura Y, Sakaguchi K, Tsuruta T, Hibi H

    96th General Session & Exhibition of the IADR 

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    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Country:United Kingdom  

  30. Exosomes derived from mesenchymal stem cells enhanced bone regeneration International conference

    Sakaguchi K, Sakai K, Sugimura Y, Tsuruta T, Watanabe J, Katagiri W, Hibi H

    96th General Session & Exhibition of the IADR 

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    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Venue:London   Country:United Kingdom  

  31. ビスホスホネート関連顎骨壊死に対する間葉系幹細胞由来エクソソームを用いた治療の可能性

    渡邊純奈,酒井陽,岡部一登,若山有紀子,坂口晃平,鶴田剛士,日比英晴

    第72回日本口腔科学会 

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    Event date: 2018.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  32. 骨髄由来間葉系幹細胞が分泌するエクソソームによる新たな骨再生

    坂口晃平,酒井陽,片桐渉,若山有紀子,鶴田剛士,渡邊純奈,日比英晴

    第17回日本再生医療学会 

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    Event date: 2018.3

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  33. 1歳男児の下顎骨に生じたランゲルハンス細胞組織球症の1例

    下島千明,酒井陽,山本憲幸,日比英晴

    第36回日本口腔腫瘍学会 

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    Event date: 2018

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  34. Epiprofin is a multi-functional factor essential to promote dental epithelial stem cell commitment to the ameloblast lineage and its proliferation and differentiation International conference

    Yoshihiko Yamada, Kiyoshi Sakai , Yuta Chiba, Bing He, Darius Mahboubi, Craig Rhodes, Yasuo Yoshitomi, Satoshi Fukumoto, Takashi Nakamura

    The 2017 Japan-NIH Joint Symposium 

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    Event date: 2017

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

    Country:Japan  

  35. Epiprofin and T-box1 regulate the ameloblast linage development International conference

    Yuta Chiba, Kiyoshi Sakai, Tomoko Ikeuchi, Keigo Yoshizaki, Darius Mahboubi, and Yoshihiko Yamada

    IADR/AADR/CADR General Session & Exhibition 

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    Event date: 2017

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  36. ラット末梢性嚥下障害モデルの確立と乳歯歯髄幹細胞由来成長因子による治療効果の検討

    鶴田剛士,片桐渉,大杉将嗣,酒井陽,若山有紀子,坂口晃平,渡邊純奈,日比英晴

    第16回日本再生医療学会 

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    Event date: 2017

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  37. ラット末梢性嚥下障害モデルを用いた乳歯歯髄幹細胞由来成長因子の治療効果の検討

    鶴田剛士,片桐渉,大杉将嗣,酒井陽,若山有紀子,坂口晃平,渡邊純奈,日比英晴

    第71回日本口腔科学会 

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    Event date: 2017

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  38. 乳歯歯髄幹細胞由来成長因子は神経の血管新生を介してラット末梢性嚥下障害を改善する

    鶴田剛士,酒井陽,片桐渉,大杉将嗣,椙村有紀子,坂口晃平,渡邊純奈,日比英晴

    第62回日本口腔外科学会 

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    Event date: 2017

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  39. 乳歯歯髄幹細胞由来培養上清を用いた末梢神経再生治療の検討

    椙村有紀子,酒井陽,坂口晃平,鶴田剛士,渡邊純奈,片桐渉,日比英晴

    第62回日本口腔外科学会 

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    Event date: 2017

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  40. 他家骨髄由来間葉系細胞の移植による骨再生の検討

    渡邊純奈,片桐渉,大杉将嗣,酒井陽,岡部一登,椙村有紀子,坂口晃平,鶴田剛士,外山直人,日比英晴

    第38回日本口腔インプラント学会中部支部学術大会 

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    Event date: 2017

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  41. 歯原性上皮細胞のエナメル芽細胞への分化におけるEpiprofinとT-box1の役割

    酒井陽, 吉崎恵悟, 千葉雄太, 池内友子, 山本朗仁, 日比英晴, 山田吉彦.

    第58回歯科基礎医学会学術大会 

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    Event date: 2016.8

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  42. 骨髄間葉系幹細胞由来培養上清を模倣した成長因子混合剤による歯周組織再生

    坂口晃平,片桐渉,大杉将嗣,酒井陽,椙村有紀子,鶴田剛士,渡邊純奈,日比英晴

    第61回日本口腔外科学会 

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    Event date: 2016

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  43. ラット末梢性嚥下障害モデルにおける乳歯歯髄幹細胞由来成長因子による治療効果の検討

    鶴田剛士,片桐渉,大杉将嗣,酒井陽,椙村有紀子,坂口晃平,渡邊純奈,日比英晴

    第61回日本口腔外科学会 

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    Event date: 2016

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  44. Interactions of Epiprofin and T-box1 in Enamel Epithelial Development International conference

    K. Sakai, K. Yoshizaki, B. He, Y. Yamada

    93th IADR/AADR/CADR 

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    Event date: 2015.3

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  45. Genetic and Functional Interactions of Epiprofin and T-box1 in Enamel Epithelial Development International conference

    K. Sakai, K. Yoshizaki, B. He, Y. Yamada

    NIH-Japan-JSPS Symposium 

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    Event date: 2014.10

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  46. 脊髄損傷における歯髄幹細胞の多面的神経再生効果 Invited

    酒井陽

    第11回日本再生医療学会総会 若手研究奨励賞 受賞者講演 

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    Event date: 2012.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  47. Engrafted dental pulp stem cells promoted functional recovery of completely transected rat spinal cord International conference

    K. Sakai, A. Yamamoto, K. Matsubara, H. Hibi, M. Ueda

    9th International Society Stem Cell Research 

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    Event date: 2011.6

    Language:English   Presentation type:Poster presentation  

    Country:Canada  

  48. Transplantation of dental pulp stem cells in spinal cord injury

    Sakai K, Matsubara K, Yamamoto A, Ueda M.

    The Third Symposium of Young Researchers - Innovativative MEMS design and the biomedical application 

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    Event date: 2010.12

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  49. Transplantation of dental pulp stem cells in spinal cord injury International conference

    K. Sakai, K. Matsubara, A. Yamamoto, M. Yamagata, M. Ueda

    2010 International Symposium on Micro-Nano Mechatronics and Human Science 

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    Event date: 2010.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  50. ラット脊髄完全切断モデルにおけるヒト歯髄細胞移植効果の検討

    酒井陽,松原弘記,山本朗仁,日比英晴,山形まり,上田実

    第52回歯科基礎医学会学術大会・総会 

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    Event date: 2010.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  51. 脱落乳歯および智歯(親知らず)由来の歯髄幹細胞による神経再生治療

    酒井陽,松原弘記,山本朗仁,日比英晴,山田陽一,今釜史郎,若尾典充,田内亮,上田実

    第31回日本炎症・再生医学会 

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    Event date: 2010.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  52. Transplantation of dental pulp stem cells in spinal cord injury International conference

    K. Sakai, A. Yamamoto, H. Hibi, Y. Yamada, M. Fujio, M. Yamagata, and M. Ueda

    88th International Association for Dental Research 

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    Event date: 2010.7

    Language:English   Presentation type:Poster presentation  

    Country:Spain  

  53. Transplantation of human dental pulp stem cells after complete transection of the rat spinal cord.

    Sakai K, Yamamoto A, Hibi H, Yamada Y, Yamagata M, Fujio M, Tauchi R, Wakao N, Imagama S, Ueda M.

    第9回日本再生医療学会総会 

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    Event date: 2010.3

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  54. Transplantation of human dental pulp stem cells in complete transaction of the rat spinal cord.

    Sakai K, Yamamoto A, Hibi H, Yamagata M, Fujio M, Ueda M.

    第2回NAGOYAグローバルリトリート名古屋大学医学部グローバルCOEプログラム 

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    Event date: 2010.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  55. ロッキングプレートによる矯正用アンカーの臨床統計的検討

    酒井陽,日比英晴,小田知生,服部宇,上田実

    第19回日本学変形症学会総会 

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    Event date: 2009.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  56. 多発性骨髄腫に対するビスフォスフォネート投与に関連したと考えられる上顎骨壊死の 1例

    酒井陽,片桐渉,服部宇,山田陽一,金山健夫,日比英晴,上田実

    第50回日本口腔科学会中部地方会 

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    Event date: 2007.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

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KAKENHI (Grants-in-Aid for Scientific Research) 6

  1. 放射線性萎縮モデルにおける唾液腺幹細胞再生メカニズムの分子基盤

    Grant number:21K10067  2021.4 - 2024.3

    酒井 陽

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  2. Cascaded bone regeneration method with extracellular vesicles prepared for different purposes under variable culture environment

    Grant number:19H03851  2019.4 - 2024.3

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

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    Authorship:Coinvestigator(s) 

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  3. エクソソームによる放射線性顎骨壊死の治療法開発と機序解明

    Grant number:19K10264  2019.4 - 2022.3

    岡部 一登

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    Authorship:Coinvestigator(s) 

    放射線治療は頭頸部がんに対して高い治療効果を有するが、口腔粘膜炎や口腔乾燥等の有害事象を必発する。特に晩期に発症する顎骨壊死は摂食障害や発音障害、審美障害をもたらし、著しくQOLを低下させる。しかしながら、顎骨壊死に対する治療法は未だ確立されておらず、放射線治療を推し進める上で解決しなければならない問題となっている。昨今、治療困難であった重篤な疾患に対して、間葉系幹細胞を由来とするエクソソームによる治療効果が注目されている。本研究では、さらに高い再生能力を持つ歯髄幹細胞を由来とするエクソソームに着目した放射線性顎骨壊死の新規治療法を開発し、発症機序の解明を図る。
    放射線治療は頭頸部がんに対して高い治療効果を有するが,口腔粘膜炎や口腔乾燥等の有害事象を必発する.特に晩期に発症する顎骨壊死(ORN)は著しくQOLを低下させるにもかかわらず,未だ治療法は確立していない.本研究の目的は,ヒト歯髄幹細胞(DPSCs)由来エクソソーム を用いた治療法を開発し,ORNの発症機序を解明することである.
    ORNの発症機序として,骨髄内の間葉系幹細胞(MSCs)の機能低下が指摘されている.本研究では,まず放射線照射したラットMSCsの遊走能,増殖能,分化能を評価し,放射線照射しなかったラット MSCsと比較して,いずれも低下していることを確認した.
    次いで,エクソソームはDPSCsの培養上清から超遠心法により分離した.粒径は約100nmであり,ウエスタンブロット法で特異的表面抗原であるCD63,CD81,CD9を確認した.また透過型電子顕微鏡により形態学的評価を実施した.定量RT-PCR法ではアポトーシス抑制や血管新生,抗炎症作用に関与する関連遺伝子を同定した.
    現在は,放射線照射したMSCsとDPSCs由来エクソソームとの共培養により,その効果に関する評価を開始した.評価項目として,多分化能,細胞増殖能,細胞遊走能,関連遺伝子の発現量の変化を設定しており,放射線照射したMSCs単独を対照群として比較する予定である.
    また並行して,ラットORNモデルの作製を試みているが,安定したモデルの確立に至っていない.確立したのちにDPSCs由来エクソソームを投与し,その治療効果を形態学および放射線学,組織学的に評価する予定である.
    本研究はin vitro実験およびin vivo実験に大別される.in vitor実験の進捗状況としては概ね順調であると考えているが,in vivo実験の要となるラットORNモデルの確立に至っていないことが「やや遅れている」と判断した最大の理由である.過去の報告を参考にモデルを作製したが,安定した結果が得られていない.現在は,テクニカルエラー等の問題点の確認作業を実施している.
    解決すべき研究の課題はラットORNモデルの確立である.すでに実施しているが,共同研究者の助言をいただき,早急に問題点を解決する予定である.場合によっては,他の報告を参考にラットORNモデルの作製手順を刷新する予定である.
    ラットORNモデルが確立し,DPSCs由来エクソソーム の有効性をin vitro実験およびin vivo実験で示すことができれば,DPSCsをマイクロアレイにより網羅的に解析する予定である.

  4. 幹細胞由来エクソソームによる新規唾液腺組織再生法の開発

    Grant number:19K19191  2019.4 - 2021.3

    若手研究

    酒井 陽

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    ヒトの体には不完全ながら修復・再生能力が備わっている。皮膚損傷や骨折などでは、自らの治癒能力を駆使して組織修復を行うが,失った組織や臓器が修復・再生されることはほとんどない。私たちはこれまでの研究で、損傷した組で重要な役割を果たすと考えられる幹細胞由来エクソソームに含まれるいくつかのmicro RNA(miRNA)を同定した。それらのmiRNA は組織が損傷していく過程で幹細胞の老化抑制,損傷細胞の生存率促進に関与し、幹細胞の“若返り”に関わっている可能性が考えられる。本研究では、幹細胞由来エクソソームを用いたシェーグレン症候群モデルマウスに対する損傷組織再生法の開発することを目的とする。
    ヒトの体には不完全ながら修復・再生能力が備わっている。皮膚損傷や骨折などでは、自らの治癒能力を駆使して組織修復を行う。しかしながら失った組織や臓器が修復・再生されることはほとんどない。現在、超高齢者社会において、高齢者の多くは口腔乾燥症状(ドライマウス)を示し、虫歯、細菌感染、嚥下障害さらにはQOLの低下などの口腔乾燥症を引き起こす。現在の口腔乾燥症の治療法は対症的であり、唾液腺機能障害を修復することはできない。唾液を産生する唾液腺には組織を構成する細胞を供給する源となる幹細胞が存在するが、老化に伴い様々な組織に存在する組織幹細胞の機能が低下していることが報告されている。しかしながら、唾液腺幹細胞については不明な点が多く、唾液腺幹細胞と加齢に伴う唾液腺の機能低下との関係については解明されていない。そこで本研究では、内在性唾液腺幹細胞および前駆細胞に着目し、加齢に伴う唾液腺幹細胞の老化機構の解明および幹細胞由来エクソソームによる老化抑制機構を検討し、内在性唾液腺幹細胞および前駆細胞の新たな再生機序を構築することを目的とする。 歯科領域において、難病にも指定されているシェーグレン症候群は自己免疫疾患とされ、慢性化した病態であり修復・再生不可能な組織であるとされる。私たちはこれまでの研究で、損傷した組織で重要な役割を果たすと考えられる幹細胞由来エクソソームに含まれるいくつかのmicro RNA (miRNA)を同定した。それらのmiRNAは組織が損傷していく過程で幹細胞の老化抑制,損傷細胞の生存率促進に関与し、幹細胞の“若返り”に関わっている可能性が考えられる。今年度本研究では、幹細胞由来エクソソームの老化抑制が抑制していることを示した。国際学会でのポスター発表をした。現在は次の段階に入り、メカニズムの解析を進行中である。
    老化細胞の老化予防は示されたが、メカニズムの解析が遅れている。
    ①幹細胞由来エクソソームの老化抑制機構の解明、②エクソソームmiRNAが損傷細胞に与える影響の解明、③幹細胞由来エクソソームを用いたシェーグレン症候群モデルマウスに対する損傷組織再生法の開発することを予定している。

  5. 骨髄間葉系細胞による顎骨再生療法の評価と臨床展開

    2017 - 2019

    科学研究費補助金  再生医療等安全性確保に従って実施する臨床研究

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    Authorship:Coinvestigator(s) 

  6. Mechanism of regulation of dental epithelial stem cell differentiation by transcription factor complexes

    Grant number:16K20569  2016.4 - 2020.3

    SAKAI KIYOSHI

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    Authorship:Principal investigator 

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    The human body is equipped with the ability to repair and regenerate, albeit imperfectly. In the case of skin injuries and fractures, we use our healing abilities to repair tissues. However, lost tissues and organs are rarely repaired or regenerated. In the dental field, the enamel of human teeth is a tissue that cannot be repaired or regenerated. We identified T-Box1 (Tbx1), which complexes with the transcription factor Epiprofin (Epfn), an essential factor for ameloblast differentiation; the Epfn-Tbx1 complex is involved in ameloblast differentiation during dental epithelial cell differentiation and may be involved in determining the fate of tooth epithelial cells.

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