2021/12/27 更新

写真a

アキヤマ ケンタロウ
秋山 謙太郎
AKIYAMA Kentaro
所属
岡山大学病院 講師
職名
講師
外部リンク

学位

  • 歯学博士 ( 2005年3月   岡山大学 )

  • 博士(歯学) ( 2005年3月   岡山大学大学院医歯薬学総合研究科 )

研究キーワード

  • 間葉系幹細胞

  • 自己免疫疾患

  • 免疫寛容

  • 組織再生

研究分野

  • ライフサイエンス / 補綴系歯学  / 組織再生

学歴

  • 岡山大学    

    - 2005年3月

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  • 岡山大学   Dental School  

    - 2001年3月

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経歴

  • 岡山大学   講師

    2014年4月 - 現在

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  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   助教

    2012年4月 - 2014年3月

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  • 南カリフォルニア大学   Reaserch associate

    2009年9月 - 2012年3月

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  • 南カリフォルニア大学   Post docteal fellow

    2006年9月 - 2009年8月

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  • 岡山大学   医員

    2005年4月 - 2006年8月

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  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   PhD

    2001年4月 - 2005年3月

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▼全件表示

所属学協会

  • International Society for Stem cell Research

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  • International association of Dental Research

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  • 日本口腔インプラント学会

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  • 日本骨免疫学会

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  • 日本補綴歯科学会

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委員歴

  • 日本補綴歯科学会 中国四国支部   代議員  

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    団体区分:学協会

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  • 日本口腔インプラント学会   研究推進委員  

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    団体区分:学協会

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  • 岡山大学   共用・総合試験委員CBT部会委員  

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  • 岡山大学   労働安全衛生委員会委員  

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  • 岡山大学   歯学部先端領域研究センター運営会議委員  

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  • 岡山大学   公募問題作成部会委員  

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  • 日本口腔インプラント学会   中国・四国支部代議員  

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  • 日本口腔インプラント学会   中央選挙管理委員会  

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論文

  • Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo. 国際誌

    Hai Thanh Pham, Mitsuaki Ono, Emilio Satoshi Hara, Ha Thi Thu Nguyen, Anh Tuan Dang, Hang Thuy Do, Taishi Komori, Ikue Tosa, Yuri Hazehara-Kunitomo, Yuya Yoshioka, Yasutaka Oida, Kentaro Akiyama, Takuo Kuboki

    Materials (Basel, Switzerland)   14 ( 1 )   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

    DOI: 10.3390/ma14010208

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  • Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model. 国際誌

    Kyaw Thu Aung, Kentaro Akiyama, Masayoshi Kunitomo, Aung Ye Mun, Ikue Tosa, Ha Thi Thu Nguyen, Jiewen Zhang, Teisaku Kohno, Mitsuaki Ono, Emilio Satoshi Hara, Takuo Kuboki

    International journal of molecular sciences   21 ( 21 )   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

    DOI: 10.3390/ijms21218103

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  • Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. 査読 国際誌

    Shoji Ryumon, Tatsuo Okui, Yuki Kunisada, Koji Kishimoto, Tsuyoshi Shimo, Kazuaki Hasegawa, Soichiro Ibaragi, Kentaro Akiyama, Nguyen Thi Thu Ha, Nur Mohammad Monsur Hassan, Akira Sasaki

    Oncology reports   42 ( 6 )   2611 - 2621   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Platinum‑based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum‑based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin‑induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

    DOI: 10.3892/or.2019.7367

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  • Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells 査読

    Yuri Hazehara-Kunitomo, Emilio Hara, Mitsuaki Ono, Kyaw Thu Aung, Keiko Komi, Hai Thanh Pham, Kentaro Akiyama, Masahiro Okada, Toshitaka Oohashi, Takuya Matsumoto, Takuo Kuboki

    International Journal of Molecular Sciences   20 ( 5 )   2019年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms20051097

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  • Impact of commensal flora on periodontal immune response to lipopolysaccharide. 査読 国際誌

    Fukuhara D, Irie K, Uchida Y, Kataoka K, Akiyama K, Ekuni D, Tomofuji T, Morita M

    Journal of periodontology   89 ( 10 )   1213 - 1220   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/JPER.17-0567

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  • Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment 査読

    Nguyen, H.T., Ono, M., Oida, Y., Hara, E.S., Komori, T., Akiyama, K., Nguyen, H.T.T., Aung, K.T., Pham, H.T., Tosa, I., Takarada, T., Matsuo, K., Mizoguchi, T., Oohashi, T., Kuboki, T.

    Journal of Bone and Mineral Research   34 ( 2 )   327 - 332   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jbmr.3598

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  • mTOR inhibition rescues osteopenia in mice with systemic sclerosis 査読

    Chider Chen, Kentaro Akiyama, Dandan Wang, Xingtian Xu, Bei Li, Alireza Moshaverinia, Frank Brombacher, Lingyun Sun, Songtao Shi

    JOURNAL OF EXPERIMENTAL MEDICINE   212 ( 1 )   73 - 91   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROCKEFELLER UNIV PRESS  

    Fibrillin-1 (FBN1) deficiency-induced systemic sclerosis is attributed to elevation of interleukin-4 (IL4) and TGF-beta, but the mechanism underlying FBN1 deficiency-associated osteopenia is not fully understood. We show that bone marrow mesenchymal stem cells (BMMSCs) from FBN1-deficient (Fbn1(+/-)) mice exhibit decreased osteogenic differentiation and increased adipogenic differentiation. Mechanistically, this lineage alteration is regulated by IL4/IL4R alpha-mediated activation of mTOR signaling to down-regulate RUNX2 and up-regulate PPAR gamma 2, respectively, via P70 ribosomal S6 protein kinase (P70S6K). Additionally, we reveal that activation of TGF-beta/SMAD3/SP1 signaling results in enhancement of SP1 binding to the IL4R alpha promoter to synergistically activate mTOR pathway in Fbn1(+/-) BMMSCs. Blockage of mTOR signaling by osteoblastic-specific knockout or rapamycin treatment rescues osteopenia phenotype in Fbn1(+/-) mice by improving osteogenic differentiation of BMMSCs. Collectively, this study identifies a previously unrecognized role of the FBN1/TGF-beta/IL4R alpha/mTOR cascade in BMMSC lineage selection and provides experimental evidence that rapamycin treatment may provide an anabolic therapy for osteopenia in Fbn1(+/-) mice.

    DOI: 10.1084/jem.20140643

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  • Cell-based bone regeneration for alveolar ridge augmentation - Cell source, endogenous cell recruitment and immunomodulatory function 査読

    Kaku, M., Akiba, Y., Akiyama, K., Akita, D., Nishimura, M.

    Journal of Prosthodontic Research   59 ( 2 )   96 - 112   2015年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jpor.2015.02.001

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  • Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report. 査読

    Omori K, Hanayama Y, Naruishi K, Akiyama K, Maeda H, Otsuka F, Takashiba S

    Clinical case reports   2 ( 6 )   286 - 295   2014年12月

  • 血清中ビタミンCの欠乏が原因の一つと考える歯肉増殖症患者の歯周治療経過

    河村 麻理, 大森 一弘, 秋山 謙太郎, 下江 正幸, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   33 ( 2 )   41 - 42   2014年12月

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    記述言語:日本語   出版者・発行元:岡山歯学会  

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  • Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression 査読

    Chider Chen, Kentaro Akiyama, Takayoshi Yamaza, Yong-Ouk You, Xingtian Xu, Bei Li, Yimin Zhao, Songtao Shi

    EMBO MOLECULAR MEDICINE   6 ( 3 )   322 - 334   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Bone marrow mesenchymal stem cells (BMMSCs) are capable of differentiating into multiple cell types and regulating immune cell response. However, the mechanisms that govern the immunomodulatory properties of BMMSCs are still not fully elucidated. Here we show that telomerase-deficient BMMSCs lose their capacity to inhibit T cells and ameliorate the disease phenotype in systemic sclerosis mice. Restoration of telomerase activity by telomerase reverse transcriptase (TERT) transfection in TERT-/- BMMSCs rescues their immunomodulatory functions. Mechanistically, we reveal that TERT, combined with beta-catenin and BRG1, serves as a transcriptional complex, which binds the FAS ligand (FASL) promoter to upregulate FASL expression, leading to an elevated immunomodulatory function. To test the translational value of these findings in the context of potential clinical therapy, we used aspirin treatment to upregulate telomerase activity in BMMSCs, and found a significant improvement in the immunomodulatory capacity of BMMSCs. Taken together, these findings identify a previously unrecognized role of TERT in improving the immunomodulatory capacity of BMMSCs, suggesting that aspirin treatment is a practical approach to significantly reduce cell dosage in BMMSC-based immunotherapies.

    DOI: 10.1002/emmm.201303000

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  • Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold 査読

    Alireza Moshaverinia, Chider Chen, Xingtian Xu, Kentaro Akiyama, Sahar Ansari, Homayoun H. Zadeh, Songtao Shi

    TISSUE ENGINEERING PART A   20 ( 3-4 )   611 - 621   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT, INC  

    DOI: 10.1089/ten.TEA.2013.0229

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  • Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in β-tricalcium phosphate. 査読

    Ono M, Sonoyama W, Yamamoto K, Oida Y, Akiyama K, Shinkawa S, Nakajima R, Pham HT, Hara ES, Kuboki T

    Cells, tissues, organs   199 ( 4 )   249 - 255   2014年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000369061

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  • 抜歯窩から採取した未分化間葉系幹細胞

    Journal of Dental Research   93 ( 11 )   1133 - 1140   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1177/0022034514549377

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  • Immunotherapy in Transplantation 査読

    Kentaro Akiyama, Emilio Hara Satoshi, Takuo Kuboki

    Stem Cell Biology and Tissue Engineering in Dental Sciences   831   2014年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    DOI: 10.1016/B978-0-12-397157-9.00068-0

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  • Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration 査読

    Alireza Moshaverinia, Xingtian Xu, Chider Chen, Kentaro Akiyama, Malcolm L. Snead, Songtao Shi

    ACTA BIOMATERIALIA   9 ( 12 )   9343 - 9350   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-beta 1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-beta 1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (p < 0.05). Taken together, these results suggest that RGD-modified alginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.actbio.2013.07.023

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  • Ossifying fibroma tumor stem cells are maintained by epigenetic regulation of a TSP1/TGF-β/SMAD3 autocrine loop. 査読

    Qin H, Qu C, Yamaza T, Yang R, Lin X, Duan XY, Akiyama K, Liu Y, Zhang Q, Chen C, Chen Y, Qi HH, Feng XH, Le AD, Shi S

    Cell stem cell   13 ( 5 )   577 - 589   2013年11月

  • Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering 査読

    Alireza Moshaverinia, Chider Chen, Kentaro Akiyama, Xingtian Xu, Winston W. L. Chee, Scott R. Schricker, Songtao Shi

    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A   101 ( 11 )   3285 - 3294   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Bone grafts are currently the major family of treatment options in modern reconstructive dentistry. As an alternative, stem cell-scaffold constructs seem to hold promise for bone tissue engineering. However, the feasibility of encapsulating dental-derived mesenchymal stem cells in scaffold biomaterials such as alginate hydrogel remains to be tested. The objectives of this study were, therefore, to: (1) develop an injectable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the cell viability and osteogenic differentiation of the stem cells in the microbeads both in vitro and in vivo. Microbeads with diameters of 1 +/- 0.1 mm were fabricated with 2 x 10(6) stem cells/mL of alginate. Microbeads containing PDLSCs, GMSCs, and human bone marrow mesenchymal stem cells as a positive control were implanted subcutaneously and ectopic bone formation was analyzed by micro CT and histological analysis at 8-weeks postimplantation. The encapsulated stem cells remained viable after 4 weeks of culturing in osteo-differentiating induction medium. Scanning electron microscopy and X-ray diffraction results confirmed that apatitic mineral was deposited by the stem cells. In vivo, ectopic mineralization was observed inside and around the implanted microbeads containing the immobilized stem cells. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in alginate microbeads provides a promising strategy for bone tissue engineering. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3285-3294, 2013.

    DOI: 10.1002/jbm.a.34546

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  • Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering 査読

    Alireza Moshaverinia, Sahar Ansari, Chider Chen, Xingtian Xu, Kentaro Akiyama, Malcolm L. Snead, Homayoun H. Zadeh, Songtao Shi

    BIOMATERIALS   34 ( 28 )   6572 - 6579   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Recently, it has been shown that tethered anti-BMP2 monoclonal antibodies (mAbs) can trap BMP ligands and thus provide BMP inductive signals for osteo-differentiation of progenitor cells. The objectives of this study were to: (1) develop a co-delivery system based on murine anti-BMP2 mAb-loaded alginate microspheres encapsulating human bone marrow mesenchymal stem cells (hBMMSCs); and (2) investigate osteogenic differentiation of encapsulated stem cells in alginate microspheres in vitro and in vivo. Alginate microspheres of 1 +/- 0.1 mm diameter were fabricated with 2 x 10(6) hBMMSCs per mL of alginate. Critical-size calvarial defects (5 mm diameter) were created in immune-compromised mice and alginate microspheres preloaded with anti-BMP mAb encapsulating hBMMSCs were transplanted into defect sites. Alginate microspheres pre-loaded with isotype-matched non-specific antibody were used as the negative control. After 8 weeks, micro CT and histologic analyses were used to analyze bone formation. In vitro analysis demonstrated that anti-BMP2 mAbs tethered BMP2 ligands that can activate the BMP receptors on hBMMSCs. The co-delivery system described herein, significantly enhanced hBMMSC-mediated osteogenesis, as confirmed by the presence of BMP signal pathway-activated osteoblast determinants Runx2 and ALP. Our results highlight the importance of engineering the microenvironment for stem cells, and particularly the value of presenting inductive signals for osteo-differentiation of hBMMSCs by tethering BMP ligands using mAbs. This strategy of engineering the microenvironment with captured BMP signals is a promising modality for repair and regeneration of craniofacial, axial and appendicular bone defects. (C) 2013 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2013.05.048

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  • Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway 査読

    Ikiru Atsuta, Shiyu Liu, Yasuo Miura, Kentaro Akiyama, Chider Chen, Ying An, Songtao Shi, Fa-Ming Chen

    STEM CELL RESEARCH & THERAPY   4 ( 5 )   111   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Introduction: Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases traditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue damage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone disease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and metastasis.
    Methods: In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of intravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether Fas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells.
    Results: In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-Lhigh MSCs) showed remarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting tumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys. In addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with Fas-Lhigh MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced apoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells. In contrast, Fas-Lnull MSCs promote MM growth.
    Conclusions: These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based inhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the levels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth.

    DOI: 10.1186/scrt322

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  • IFN-γ and TNF-α synergistically induce mesenchymal stem cell impairment and tumorigenesis via NFκB signaling. 査読

    Wang L, Zhao Y, Liu Y, Akiyama K, Chen C, Qu C, Jin Y, Shi S

    Stem cells (Dayton, Ohio)   31 ( 7 )   1383 - 1395   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/stem.1388

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  • Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow 査読

    Valerie A. Siclari, Ji Zhu, Kentaro Akiyama, Fei Liu, Xianrong Zhang, Abhishek Chandra, Hyun-Duck Nah, Songtao Shi, Ling Qin

    BONE   53 ( 2 )   575 - 586   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method isolates only mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express common mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared with their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared with young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies. (C) 2012 Elsevier Inc. All rights reserved.

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  • A subset of IL-17(+) mesenchymal stem cells possesses anti-Candida albicans effect 査読

    Ruili Yang, Yi Liu, Peyman Kelk, Cunye Qu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta, WanJun Chen, Yanheng Zhou, Songtao Shi

    CELL RESEARCH   23 ( 1 )   107 - 121   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INST BIOCHEMISTRY & CELL BIOLOGY  

    Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties, such as upregulation of Foxp3(+) regulatory T cells (Tregs) and downregulation of Th17 cells. However, it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function. Here, we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs, downregulate Th17 cells, or ameliorate disease phenotypes in a colitis mouse model. Mechanistically, we reveal that IL-17, produced by these MSCs, activates the NF kappa B pathway to downregulate TGF-beta production in MSCs, resulting in abolishment of MSC-based immunomodulation. Furthermore, we show that NF kappa B is able to directly bind to TGF-beta promoter region to regulate TGF-beta expression in MSCs. Moreover, these IL-17(+) MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C. albicans-infected mice. In summary, this study shows that MSCs contain an IL-17(+) subset capable of inhibiting C. albicans growth, but attenuating MSC-based immunosuppression via NF kappa B-mediated downregulation of TGF-beta.

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  • Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine 査読

    Lan Ma, Yusuke Makino, Haruyoshi Yamaza, Kentaro Akiyama, Yoshihiro Hoshino, Guangtai Song, Toshio Kukita, Kazuaki Nonaka, Songtao Shi, Takayoshi Yamaza

    PLOS ONE   7 ( 12 )   e51777   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED) with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25-30 months) (SHED-Cryo) owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh). To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine. Citation: Ma L, Makino Y, Yamaza H, Akiyama K, Hoshino Y, et al. (2012) Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine. PLoS ONE 7(12): e51777. doi:10.1371/journal.pone.0051777

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  • Technetium-99 Conjugated with Methylene Diphosphonate Ameliorates Ovariectomy-Induced Osteoporotic Phenotype without Causing Osteonecrosis in the Jaw 査読

    Yinghua Zhao, Lei Wang, Yi Liu, Kentaro Akiyama, Chider Chen, Ikiru Atsuta, Tao Zhou, Xiaohong Duan, Yan Jin, Songtao Shi

    CALCIFIED TISSUE INTERNATIONAL   91 ( 6 )   400 - 408   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Technetium-99 conjugated with methylene diphosphonate (Tc-99-MDP) is a novel bisphosphonate derivative without radioactivity and has been successfully used to treat arthritis in China for years. Since bisphosphonate therapy has the potential to induce bisphosphonate-related osteonecrosis of the jaw (BRONJ), we examined whether Tc-99-MDP represents a new class of bisphosphonate for antiresorptive therapy to ameliorate estrogen deficiency-induced bone resorption with less risk of causing BRONJ. We showed that Tc-99-MDP-treated, ovariectomized (OVX) mice had significantly improved bone mineral density and trabecular bone volume in comparison to the untreated OVX group by inhibiting osteoclasts and enhancing osteogenic differentiation of bone marrow mesenchymal stem cells. To determine the potential of inducing BRONJ, Tc-99-MDP/dexamethasone (Dex) or zoledronate/Dex was administered into C57BL/6J mice via the tail vein, followed by extraction of maxillary first molars. Interestingly, Tc-99-MDP treatment showed less risk to induce osteonecrosis in the maxillary bones compared to zoledronate treatment group, partially because Tc-99-MDP neither suppressed adaptive regulatory T cells nor activated the inflammatory T-helper-producing interleukin-17 cells. Taken together, our findings demonstrate that Tc-99-MDP therapy may be a promising approach in the treatment of osteoporosis with less risk of causing BRONJ.

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  • Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study 査読

    Alireza Moshaverinia, Chider Chen, Kentaro Akiyama, Sahar Ansari, Xingtian Xu, Winston W. Chee, Scott R. Schricker, Songtao Shi

    JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE   23 ( 12 )   3041 - 3051   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The objectives of this study were to: (1) develop an injectable and biodegradable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the stem cell viability, and osteogenic differentiation of the stem cells in vitro. Stem cells were encapsulated using alginate hydrogel. The stem cell viability, proliferation and differentiation to adipogenic and osteogenic tissues were studied. To investigate the expression of both adipogenesis and ontogenesis related genes, the RNA was extracted and RT-PCR was performed. The degradation behavior of hydrogel based on oxidized sodium alginate with different degrees of oxidation was studied in PBS at 37 A degrees C as a function of time by monitoring the changes in weight loss. The swelling kinetics of alginate hydrogel was also investigated. The results showed that alginate is a promising candidate as a non-toxic scaffold for PDLSCs and GMSCs. It also has the ability to direct the differentiation of these stem cells to osteogenic and adipogenic tissues as compared to the control group in vitro. The encapsulated stem cells remained viable in vitro and both osteo-differentiated and adipo-differentiated after 4 weeks of culturing in the induction media. It was found that the degradation profile and swelling kinetics of alginate hydrogel strongly depends on the degree of oxidation showing its tunable chemistry and degradation rate. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in the alginate microspheres provides a promising strategy for bone tissue engineering.

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  • Characterization of bone marrow derived mesenchymal stem cells in suspension 査読

    Kentaro Akiyama, Yong-Ouk You, Takayoshi Yamaza, Chider Chen, Liang Tang, Yan Jin, Xiao-Dong Chen, Stan Gronthos, Songtao Shi

    STEM CELL RESEARCH & THERAPY   3 ( 5 )   40   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Introduction: Bone marrow mesenchymal stem cells (BMMSCs) are a heterogeneous population of postnatal precursor cells with the capacity of adhering to culture dishes generating colony-forming unit-fibroblasts (CFU-F). Here we identify a new subset of BMMSCs that fail to adhere to plastic culture dishes and remain in culture suspension (S-BMMSCs).
    Methods: To catch S-BMMSCs, we used BMMSCs-produced extracellular cell matrix (ECM)-coated dishes. Isolated S-BMMSCs were analyzed by in vitro stem cell analysis approaches, including flow cytometry, inductive multiple differentiation, western blot and in vivo implantation to assess the bone regeneration ability of S-BMMSCs. Furthermore, we performed systemic S-BMMSCs transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.
    Results: S-BMMSCs are capable of adhering to ECM-coated dishes and showing mesenchymal stem cell characteristics with distinction from hematopoietic cells as evidenced by co-expression of CD73 or Oct-4 with CD34, forming a single colony cluster on ECM, and failure to differentiate into hematopoietic cell lineage. Moreover, we found that culture-expanded S-BMMSCs exhibited significantly increased immunomodulatory capacities in vitro and an efficacious treatment for SLE-like MRL/lpr mice by rebalancing regulatory T cells (Tregs) and T helper 17 cells (Th17) through high NO production.
    Conclusions: These data suggest that it is feasible to improve immunotherapy by identifying a new subset BMMSCs.

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  • Stem cells in dentistry - Part II: Clinical applications 査読

    Hiroshi Egusa, Wataru Sonoyama, Masahiro Nishimura, Ikiru Atsuta, Kentaro Akiyama

    JOURNAL OF PROSTHODONTIC RESEARCH   56 ( 4 )   229 - 248   2012年10月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    New technologies that facilitate solid alveolar ridge augmentation are receiving considerable attention in the field of prosthodontics because of the growing requirement for esthetic and functional reconstruction by dental implant treatments. Recently, several studies have demonstrated potential advantages for stem-cell-based therapies in regenerative treatments. Mesenchymal stem/stromal cells (MSCs) are now an excellent candidate for tissue replacement therapies, and tissue engineering approaches and chair-side cellular grafting approaches using autologous MSCs represent the clinical state of the art for stem-cell-based alveolar bone regeneration. Basic studies have revealed that crosstalk between implanted donor cells and recipient immune cells plays a key role in determining clinical success that may involve the recently observed immunomodulatory properties of MSCs. Part II of this review first overviews progress in regenerative dentistry to consider the implications of the stem cell technology in dentistry and then highlights cutting-edge stem-cell-based alveolar bone regenerative therapies. Factors that affect stem-cell-based bone regeneration as related to the local immune response are then discussed. Additionally, pre-clinical stem cell studies for the regeneration of teeth and other oral organs as well as possible applications of MSC-based immunotherapy in dentistry are outlined. Finally, the marketing of stem cell technology in dental stem cell banks with a view toward future regenerative therapies is introduced. (C) 2012 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved.

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  • Stem cells in dentistry - Part I: Stem cell sources 査読

    Hiroshi Egusa, Wataru Sonoyama, Masahiro Nishimura, Ikiru Atsuta, Kentaro Akiyama

    JOURNAL OF PROSTHODONTIC RESEARCH   56 ( 3 )   151 - 165   2012年7月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra-and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties. (C) 2012 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved.

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  • Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis 査読

    Kentaro Akiyama, Chider Chen, DanDan Wang, Xingtian Xu, Cunye Qu, Takayoshi Yamaza, Tao Cai, WanJun Chen, Lingyun Sun, Songtao Shi

    CELL STEM CELL   10 ( 5 )   544 - 555   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) yields therapeutic benefit for a variety of autoimmune diseases, but the underlying mechanisms are poorly understood. Here we show that in mice systemic infusion of BMMSCs induced transient T cell apoptosis via the FAS ligand (FASL)dependent FAS pathway and could ameliorate disease phenotypes in fibrillin-1 mutated systemic sclerosis (SS) and dextran-sulfate-sodium-induced experimental colitis. FASL(-/-) BMMSCs did not induce T cell apoptosis in recipients, and could not ameliorate SS and colitis. Mechanistic analysis revealed that FAS-regulated monocyte chemotactic protein 1 (MCP-1) secretion by BMMSCs recruited T cells for FASL-mediated apoptosis. The apoptotic T cells subsequently triggered macrophages to produce high levels of TGF beta, which in turn led to the upregulation of Ca4(+)CD25(+)Foxp3(+) regulatory T cells and, ultimately, immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via FAS/FASL to induce T cell apoptosis.

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  • Double Allogenic Mesenchymal Stem Cells Transplantations Could Not Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus 査読

    Dandan Wang, Kentaro Akiyama, Huayong Zhang, Takayoshi Yamaza, Xia Li, Xuebing Feng, Hong Wang, Bingzhu Hua, Bujun Liu, Huji Xu, Wanjun Chen, Songtao Shi, Lingyun Sun

    CLINICAL & DEVELOPMENTAL IMMUNOLOGY   2012   273291   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HINDAWI PUBLISHING CORPORATION  

    The clinical trial of allogenic mesenchymal stem cells (MSCs) transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT) is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enrolled in this study, in which 30 were randomly given single MSCT, and the other 28 were given double MSCT. Patients were followed up for rates of survival, disease remission, and relapse, as well as transplantation-related adverse events. SLE disease activity index (SLEDAI) and serologic features were evaluated. Our results showed that no remarkable differences between single and double allogenic MSCT were found in terms of disease remission and relapse, amelioration of disease activity, and serum indexes in an SLE clinical trial with more than one year followup. This study demonstrated that single MSCs transplantation at the dose of one million MSCs per kilogram of body weight was sufficient to induce disease remission for refractory SLE patients.

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  • Lineage differentiation of mesenchymal stem cells from dental pulp, apical papilla, and periodontal ligament. 査読

    Akiyama K, Chen C, Gronthos S, Shi S

    Methods in molecular biology (Clifton, N.J.)   887   111 - 121   2012年

  • Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. 査読

    Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W, Wang S, Shi S

    Nature medicine   17 ( 12 )   1594 - U106   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors 査読

    Sara Parsa, Koh-ichi Kuremoto, Kerstin Seidel, Reza Tabatabai, BreAnne MacKenzie, Takayoshi Yamaza, Kentaro Akiyama, Jonathan Branch, Chester J. Koh, Denise Al Alam, Ophir D. Klein, Saverio Bellusci

    DEVELOPMENT   137 ( 22 )   3743 - 3752   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

    Rodent incisors regenerate throughout the lifetime of the animal owing to the presence of epithelial and mesenchymal stem cells in the proximal region of the tooth. Enamel, the hardest component of the tooth, is continuously deposited by stem cell-derived ameloblasts exclusively on the labial, or outer, surface of the tooth. The epithelial stem cells that are the ameloblast progenitors reside in structures called cervical loops at the base of the incisors. Previous studies have suggested that FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), is crucial for development of the epithelial stem cell population in mouse incisors. To explore the role of FGFR2b signaling during development and adult life, we used an rtTA transactivator/tetracycline promoter approach that allows inducible and reversible attenuation of FGFR2b signaling. Downregulation of FGFR2b signaling during embryonic stages led to abnormal development of the labial cervical loop and of the inner enamel epithelial layer. In addition, postnatal attenuation of signaling resulted in impaired incisor growth, characterized by failure of enamel formation and degradation of the incisors. At a cellular level, these changes were accompanied by decreased proliferation of the transit-amplifying cells that are progenitors of the ameloblasts. Upon release of the signaling blockade, the incisors resumed growth and reformed an enamel layer, demonstrating that survival of the stem cells was not compromised by transient postnatal attenuation of FGFR2b signaling. Taken together, our results demonstrate that FGFR2b signaling regulates both the establishment of the incisor stem cell niches in the embryo and the regenerative capacity of incisors in the adult.

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  • Cell-Based Immunotherapy With Mesenchymal Stem Cells Cures Bisphosphonate-Related Osteonecrosis of the Jaw-like Disease in Mice 査読

    Takashi Kikuiri, Insoo Kim, Takyoshi Yamaza, Kentaro Akiyama, Qunzhou Zhang, Yunsheng Li, Chider Chen, WanJun Chen, Songlin Wang, Anh D. Le, Songtao Shi

    JOURNAL OF BONE AND MINERAL RESEARCH   25 ( 7 )   1668 - 1679   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Patients on high-dose bisphosphonate and immunosuppressive therapy have an increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ); despite the disease severity, its pathophysiology remains unknown, and appropriate therapy is not established. Here we have developed a mouse model of BRONJ-like disease that recapitulates major clinical and radiographic manifestations of the human disease, including characteristic features of an open alveolar socket, exposed necrotic bone or sequestra, increased inflammatory infiltrates, osseous sclerosis, and radiopaque alveolar bone. We show that administration of zoledronate, a potent aminobisphosphonate, and dexamethasone, an immunosuppressant drug, causes BRONJ-like disease in mice in part by suppressing the adaptive regulatory T cells, Tregs, and activating the inflammatory T-helper-producing interleukin 17 cells, Th17. Most interestingly, we demonstrate that systemic infusion with mesenchymal stem cells (MSCs) prevents and cures BRONJ-like disease possibly via induction of peripheral tolerance, shown as an inhibition of Th17 and increase in Treg cells. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. These findings provide evidence of an immunity-based mechanism of BRONJ-like disease and support the rationale for in vivo immunomodulatory therapy using Tregs or MSCs to treat BRONJ. (C) 2010 American Society for Bone and Mineral Research.

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  • Immunomodulatory properties of stem cells from human exfoliated deciduous teeth 査読

    Takayoshi Yamaza, Akiyama Kentaro, Chider Chen, Yi Liu, Yufang Shi, Stan Gronthos, Songlin Wang, Songtao Shi

    STEM CELL RESEARCH & THERAPY   1 ( 1 )   5   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Introduction: Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a population of postnatal stem cells capable of differentiating into osteogenic and odontogenic cells, adipogenic cells, and neural cells. Herein we have characterized mesenchymal stem cell properties of SHED in comparison to human bone marrow mesenchymal stem cells (BMMSCs).
    Methods: We used in vitro stem cell analysis approaches, including flow cytometry, inductive differentiation, telomerase activity, and Western blot analysis to assess multipotent differentiation of SHED and in vivo implantation to assess tissue regeneration of SHED. In addition, we utilized systemic SHED transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.
    Results: We found that SHED are capable of differentiating into osteogenic and adipogenic cells, expressing mesenchymal surface molecules (STRO-1, CD146, SSEA4, CD73, CD105, and CD166), and activating multiple signaling pathways, including TGF beta, ERK, Akt, Wnt, and PDGF. Recently, BMMSCs were shown to possess an immunomodulatory function that leads to successful therapies for immune diseases. We examined the immunomodulatory properties of SHED in comparison to BMMSCs and found that SHED had significant effects on inhibiting T helper 17 (Th17) cells in vitro. Moreover, we found that SHED transplantation is capable of effectively reversing SLE-associated disorders in MRL/lpr mice. At the cellular level, SHED transplantation elevated the ratio of regulatory T cells (Tregs) via Th17 cells.
    Conclusions: These data suggest that SHED are an accessible and feasible mesenchymal stem cell source for treating immune disorders like SLE.

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  • Mesenchymal stem cell-mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice 査読

    Takayoshi Yamaza, Yasuo Miura, Kentaro Akiyama, Yanming Bi, Wataru Sonoyama, Stan Gronthos, WanJun Chen, Anh Le, Songtao Shi

    BLOOD   113 ( 11 )   2595 - 2604   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC HEMATOLOGY  

    Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age-related degeneration in multiple organs and benefited an increase in life span extension compared with control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor/signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice. (Blood.2009;113:2595-2604)

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  • Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo 査読

    Yosuke Okamoto, Wataru Sonoyama, Mitsuaki Ono, Kentaro Akiyama, Takuo Fujisawa, Masamitstu Oshima, Yohei Tsuchimoto, Yoshizo Matsuka, Tatsuji Yasuda, Songtao Shi, Takuo Kuboki

    JOURNAL OF ENDODONTICS   35 ( 3 )   367 - 372   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mu mol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs. (J Endod 2009;35:367-372)

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  • Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. 査読

    Yosuke Okamoto, Wataru Sonoyama, Mitsuaki Ono, Kentaro Akiyama, Takuo Fujisawa, Masamitsu Oshima, Yohei Tsuchimoto, Yoshizo Matsuka, Tatsuji Yasuda, Songtao Shi, Takuo Kuboki

    Journal of Endodontics   Vol.35 ( No.3 )   367 - 372   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mumol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs.

    DOI: 10.1016/j.joen.2008.11.024

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  • Mesenchymal Stem Cell Transplantation Reverses Multiorgan Dysfunction in Systemic Lupus Erythematosus Mice and Humans 査読

    Lingyun Sun, Kentaro Akiyama, Huayong Zhang, Takayoshi Yamaza, Yayi Hou, Shengnan Zhao, Ting Xu, Anh Le, Songtao Shi

    STEM CELLS   27 ( 6 )   1421 - 1432   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ALPHAMED PRESS  

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. Here, we reported that impairment of bone marrow mesenchymal stem cells (BMMSCs) and their associated osteoblastic niche deficiency contribute in part to the pathogenesis of SLE-like disease in MRL/lpr mice. Interestingly, allogenic BMMSC transplantation (MSCT) is capable of reconstructing the bone marrow osteoblastic niche and more effectively reverses multiorgan dysfunction when compared with medical immunosuppression with cyclophosphamide (CTX). At the cellular level, MSCT, not CTX treatment, was capable to induce osteoblastic niche reconstruction, possibly contributing to the recovery of regulatory T-cells and reestablishment of the immune homeostasis. On the basis of the promising clinical outcomes in SLE mice, we treated four CTX/glucocorticoid treatment-refractory SLE patients using allogenic MSCT and showed a stable 12-18 months disease remission in all treated patients. The patients benefited an amelioration of disease activity, improvement in serologic markers and renal function. These early evidences suggest that allogenic MSCT may be a feasible and safe salvage therapy in refractory SLE patients. STEM CELLS 2009;27:1421-1432

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  • Is aspirin treatment an appropriate intervention to osteoporosis? 査読

    Shi S, Yamaza T, Akiyama K

    Future rheumatology   3 ( 6 )   499 - 502   2008年12月

  • Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents 査読

    Takayoshi Yamaza, Yasuo Miura, Yanming Bi, Yongzhong Liu, Kentaro Akiyama, Wataru Sonoyama, Voymesh Patel, Silvio Gutkind, Marian Young, Stan Gronthos, Anh Le, Cun-Yu Wang, WanJun Chen, Songtao Shi

    PLOS ONE   3 ( 7 )   e2615   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels.
    Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced ostoeporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density.
    Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts.

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  • Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2 査読

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawakij, Kentaro Akiyama, Kengo Shimono, Masarnitsu Oshima, Takashi Nishida, Yasuhiro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    CELL TRANSPLANTATION   17 ( 1-2 )   231 - 240   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COGNIZANT COMMUNICATION CORP  

    Multiple roles have been already recognized for CCN2 in cartilage development and regeneration. However, the effects of CCN2 on bone regeneration remain to be elucidated. In this study, the utility of CCN2 on bone regeneration was examined in vitro and in vivo in combination with hydroxyapatite (HAp) as a scaffold. Human bone marrow stromal cells (hBMSCs) were isolated from human iliac bone marrow aspirates of healthy donors and expanded, and the effects of CCN2 on their proliferation and migration were examined in vitro. The proliferation of hBMSCs on a plastic or HAp plate was significantly enhanced by CCN2. Moreover, the migration of hBMSCs also dramatically increased by CCN2. Interestingly, a C-terminal signal modular fragment of CCN2 (CT-module) also enhanced the cell proliferation and migration as efficiently as the full-length CCN2. Next, in order to estimate the effect of CCN2 on the migration and survival of hBMSCs and bone formation inside the HAp scaffold in vivo, two experiments were performed. First, the porous HAp carrier was cultured with hBMSCs for a week, and the cell-scaffold hybrid was transplanted with or without CCN2 subcutaneously into immunocompromised mice. CCN2 accelerated the hBMSC-like cell migration and survival inside the porous HAp within 4 weeks after transplantation. Second, the porous HAp carrier with or without CCN2 was directly implanted into bone defects within a rabbit mandible, and bone regeneration inside was evaluated. As a result, CCN2 efficiently induced the cell invasion and bone formation inside the porous HAp scaffold. These findings suggest that CCN2 and its CT-module fragment could be useful for regeneration and reconstruction of large-scale bone defects.

    DOI: 10.3727/000000008783907143

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  • Promotion of attachment of human bone marrow stromal cells by CCN2 査読

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawaki, Kentaro Akiyama, Masamitsu Oshima, Takashi Nishida, Yasuhlro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   357 ( 1 )   20 - 25   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Cell attachment is a crucial step in tissue regeneration. In this study, human bone marrow stromal cells (hBMSCs) were isolated, and the effects of CCN2 on their attachment were examined. CCN2 significantly enhanced the hBMSC attachment, and this enhanced cell attachment was mainly regulated by the C-terminal module of CCN2. This enhancement was negated by the anti-integrin alpha(v)beta(3) antibody and p38 MAPK inhibitor, and phosphorylation of p38 MAPK was detected upon the enhanced cell attachment mediated by CCN2. We thus conclude that CCN2 enhances hBMSC attachment via integrin-p38 MAPK signal pathway. Enhanced hBMSC attachment on hydroxyapatite plates by CCN2 further indicated the utility of CCN2 in bone regeneration. (c) 2007 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2007.03.052

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  • 骨芽細胞様細胞(MC3T3E1)分化に対するチタンの影響

    秋山 謙太郎, 藤澤 拓生, 明貝 文夫, 大野 充明, 吉田 靖弘, 高柴 正悟, 鈴木 一臣, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   24回   229 - 229   2006年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨代謝学会  

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  • 骨芽細胞様細胞株(MC3T3E1細胞)の細胞接着,増殖,分化および遺伝子発現に対するチタンの影響

    秋山 謙太郎, 藤澤 拓生, 明貝 文夫, 完山 学, 吉田 靖弘, 高柴 正悟, 鈴木 一臣, 窪木 拓男

    日本口腔インプラント学会誌   19 ( 1 )   32 - 32   2006年3月

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    記述言語:日本語   出版者・発行元:(公社)日本口腔インプラント学会  

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  • Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction 査読

    M Kanyama, T Kuboki, K Akiyama, K Nawachi, FM Miyauchi, H Yatani, S Kubota, T Nakanishi, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   48 ( 10 )   723 - 730   2003年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Objective: To understand bone regeneration process after tooth extraction could be a clue to develop a new strategy for alveolar bone reconstruction. Recently, accumulated evidences support that connective tissue growth factor (CTGF) is implicated in tissue repair of many tissues. In this study, we investigated the spatial and temporal expression of CTGF in the rat tooth extraction sockets. Design: Five weeks old wild type mate rats (weighing 120 g) were used for this experiment. Expression of CTGF was determined by immunohistochemistry and in situ hybridization in the rat upper molar tooth extraction sockets at 2, 4, 7, 10 and 14 days after tooth extraction. Results: CTGF was expressed strongly in the endothelial. cells migrating into the granulation tissue at the bottom of the sockets during 4 days after tooth extraction. During the reparative process, no apparent chondrocyte-like cell appeared in the sockets, while osteoblast-like cells proliferated in the sockets with low CTGF expression at 7, 10, 14 days after extraction. As expected, no staining was observed with the preimmune rabbit IgG and CTGF sense probe. CTGF may play an important rote in angiogenesis and granulation tissue formation specifically at early heating stage after tooth extraction to initiate alveolar bone repair. Conclusion: CTGF was expressed at early heating stage of the rat tooth extraction wound. (C) 2003 Elsevier Ltd. All. rights reserved.

    DOI: 10.1016/S0003-9969(03)00153-5

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  • Cbfa1/Runx2 gene expression in articular chondrocytes of the mice temporomandibular and knee joints in vivo 査読

    T Kuboki, M Kanyama, T Nakanishi, K Akiyama, K Nawachi, H Yatani, K Yamashita, T Takano-Yamamoto, M Takigawa

    ARCHIVES OF ORAL BIOLOGY   48 ( 7 )   519 - 525   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Healthy articular cartilage is thought to be maintained by the modulation of Cbfa1 expression, although little is currently known about Cbfa1 expression in such tissues. Therefore, we examined in vivo Cbfa1 transcript levels in the temporomandibular (TM) and knee joints of 3- and 10-week-old mate ICR mice (weighing 50-70 g). A digoxigenin-11-UTP-labeled single-stranded RNA probe (0.6 kbp PstI-HindIII fragment of the 3' of untranslated region in exon 8 of mouse Cbfa1 cDNA) was prepared and in situ hybridization was performed on paraffin-embedded TM and knee joint sections. The antisense probe detected Cbfa1 transcripts in prehypertrophic chondrocytes, but not in the articular surface layer chondrocytes, of 3- and 10-week-old mice TMJs. Despite the intense Cbfa1 expression in prehypertrophic chondrocytes, articular surface layer chondrocytes of the knee joints expressed tow and undetectable level of Cbfa1 in the 3- and 10-week-old mice, respectively. These results indicate that Cbfa1 are highly expressed in the prehypertrophic chondrocytes presumably for articular tissue remodeling during the entire lifespan of the mouse, whereas Cbfa1 expression is suppressed in the articular surface chondrocytes in the adult mouse TM and knee joints to obtain the permanent cartilage phenotype. (C) 2003 Elsevier Science Ltd. All rights reserved.

    DOI: 10.1016/S0003-9969(03)00088-8

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MISC

  • 間葉系幹細胞の新しい機能-免疫調節細胞としての間葉系幹細胞-.

    秋山謙太郎, 古味佳子, 窪木拓男

    日本補綴歯科学会誌.   8 ( 4 )   346 - 353   2016年

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  • Ossifying Fibroma Tumor Stem Cells Are Maintained by Epigenetic Regulation of a TSP1/TGF-beta/SMAD3 Autocrine Loop (Retraction of vol 13, pg 577, 2013)

    Haiyan Qin, Cunye Qu, Takayoshi Yamaza, Ruili Yang, Xia Lin, Xue-Yan Duan, Kentaro Akiyama, Yi Liu, Qunzhou Zhang, Chider Chen, Yibu Chen, Hank Heng Qi, Xin-Hua Feng, Anh D. Le, Songtao Shi

    CELL STEM CELL   16 ( 5 )   569 - 569   2015年5月

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    記述言語:英語   出版者・発行元:CELL PRESS  

    DOI: 10.1016/j.stem.2015.04.016

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  • 幹細胞を用いた組織再生法の新機軸 内在性幹細胞の動員

    秋山 謙太郎, 秋葉 陽介, 秋田 大輔

    日本補綴歯科学会誌   6 ( 特別号 )   97 - 97   2014年5月

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    記述言語:日本語   出版者・発行元:(公社)日本補綴歯科学会  

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  • Efficient bone formation in swine socket-lift model using E. coli-derived rhBMP-2 adsorbed in β-TCP.

    Ono M, Sonoyama W, Yamamoto K, Oida Y, Akiyama K, Shinkawa S, Nakajima R, Pham HT, Hara ES, Kuboki T

    Cells Tissues Organs   199 ( 4 )   249 - 255   2014年

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  • Connective tissue growth factor (CTGF/CCN2) enhanced human bone marrow stromall cell attachment in vitro and migration and survival of the cells in a hydroxyapatite scaffold in vivo.

    M Ono, W Sonoyama, K Akiyama, T Fujisawa, T Nishida, M Takigawa, T Kuboki

    JOURNAL OF BONE AND MINERAL RESEARCH   20 ( 9 )   S203 - S204   2005年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC BONE & MINERAL RES  

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  • CTGF upregulation observed in the rat tooth extraction sockets.

    M Kanyama, T Kuboki, K Akiyama, F Miyauchi, K Nawachi, H Yatani, S Kubota, T Nakanishi, M Takigawa

    JOURNAL OF DENTAL RESEARCH   81   A107 - A107   2002年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

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講演・口頭発表等

  • 加齢に伴う間葉系幹細胞機能低下と骨破壊

    第130回日本補綴歯科学会学術大会  2021年6月20日 

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    会議種別:シンポジウム・ワークショップ パネル(公募)  

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受賞

  • 優秀演題賞

    2014年7月   日本骨免疫学会  

    秋山謙太郎

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共同研究・競争的資金等の研究

  • 骨髄微小環境における骨形成・吸収メカニズムの分子基盤の解明と治療戦略

    2019年 - 2022年

    大野 充昭

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    資金種別:競争的資金

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  • 薬剤関連顎骨壊死の骨髄微小環境と大腸菌由来BMP-2の応用

    2019年 - 2022年

    縄稚 久美子

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    資金種別:競争的資金

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  • 咬合メカニカルストレスによる歯周組織形成・成熟機構に立脚したバイオ人工歯根の開発

    2019年 - 2022年

    大島 正充

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    資金種別:競争的資金

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  • ステムセルエイジングの制御に向けた間葉系幹細胞未分化性維持機構の解明

    2018年 - 2020年

    窪木 拓男

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    資金種別:競争的資金

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  • 間葉系幹細胞の機能低下から見た歯周病やインプラント周囲炎発症の新規理解と対策

    2017年 - 2020年

    秋山 謙太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • BMP−2の環境選択的骨誘導/抑制メカニズムの解明・応用に基づく骨再生療法の開発

    2016年 - 2019年

    大野 充昭

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    資金種別:競争的資金

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  • HMGB1が骨髄由来間葉系幹細胞に与える影響の検討

    2016年 - 2018年

    古味 佳子

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    資金種別:競争的資金

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  • 慢性腎臓病の重症化リスク因子と透析合併感染症起因菌の同定

    2016年 - 2018年

    小山 絵理

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    資金種別:競争的資金

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  • iPS細胞樹立技術を応用した象牙芽細胞マスター遺伝子の探索

    2016年 - 2018年

    大野 充昭

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    資金種別:競争的資金

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  • 次世代歯周軟組織再生療法としての角化上皮粘膜誘導制御

    2015年 - 2019年

    前川 賢治

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    資金種別:競争的資金

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  • インプラント周囲炎の生物学的病態解明と免疫学的治療法の開発

    2015年 - 2018年

    三野 卓哉

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    資金種別:競争的資金

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  • 再生器官の発生時間軸を制御するマスター遺伝子の探索

    2015年 - 2017年

    大島 正充

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    資金種別:競争的資金

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  • ステムセルエイジングの制御に向けたアミノ酸による間葉系幹細胞未分化性維持

    2015年 - 2017年

    窪木 拓男

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    資金種別:競争的資金

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  • 歯胚発生プログラムの解明・応用に基づく歯の再生技術の開発

    2014年 - 2018年

    窪木 拓男

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    資金種別:競争的資金

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  • ホスト幹細胞集積による新規組織再生療法の開発

    2014年 - 2017年

    秋山 謙太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 難治性神経疾患の新規治療法開発-歯髄由来幹細胞の新たな生物学的機能-

    2014年 - 2016年

    秋山 謙太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • BMP-2の環境選択的な骨誘導/抑制メカニズムの解明および適応症の探索

    2013年 - 2016年

    縄稚 久美子

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    資金種別:競争的資金

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  • 新たなリプログラミング法による組織幹細胞作製技術の開発

    2013年 - 2015年

    窪木 拓男

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    資金種別:競争的資金

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  • ヒト歯髄幹細胞による自己免疫性脳炎の治療効果とそのメカニズムの検討

    2012年 - 2014年

    秋山 謙太郎

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    担当区分:研究代表者  資金種別:競争的資金

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担当授業科目

  • インプラントによる咬合再建学 (2021年度) 第4学期  - 水1

  • インプラント再生補綴学I(演習・実習) (2021年度) 特別  - その他

  • インプラント再生補綴学I(講義・演習) (2021年度) 特別  - その他

  • インプラント再生補綴学II(演習・実習) (2021年度) 特別  - その他

  • インプラント再生補綴学II(講義・演習) (2021年度) 特別  - その他

  • クラウンによる咬合再建学 (2021年度) 第2学期  - 水4

  • デジタル技術と口腔インプラントによる咬合再建手技実習 (2021年度) 第1学期  - 金5,金6,金7

  • ブリッジによる咬合再建学 (2021年度) 第3学期  - 水1

  • ブリッジによる咬合再建手技実習 (2021年度) 第3学期  - 月5,月6,月7

  • 口腔インプラント義歯学(実習(臨床実習)) (2021年度) 特別  - その他

  • 口腔インプラント義歯学(講義・演習) (2021年度) 特別  - その他

  • 口腔リハビリテーション学(実習(臨床実習)) (2021年度) 特別  - その他

  • 口腔リハビリテーション学(講義・演習) (2021年度) 特別  - その他

  • 固定性補綴装置による咬合再建手技実習 (2021年度) 第4学期  - 月5,月6,月7

  • 接着の科学と咬合再建手技実習 (2021年度) 第2学期  - 火5,火6,火7,火8

  • 顎関節症・口腔顔面痛治療学(実習(臨床実習)) (2021年度) 特別  - その他

  • 顎関節症・口腔顔面痛治療学(講義・演習) (2021年度) 特別  - その他

  • 高度補綴治療学(実習(臨床実習)) (2021年度) 特別  - その他

  • 高度補綴治療学(講義・演習) (2021年度) 特別  - その他

  • インプラントによる咬合再建学 (2020年度) 第4学期  - 水1

  • インプラント再生補綴学I(演習・実習) (2020年度) 特別  - その他

  • インプラント再生補綴学I(講義・演習) (2020年度) 特別  - その他

  • インプラント再生補綴学II(演習・実習) (2020年度) 特別  - その他

  • インプラント再生補綴学II(講義・演習) (2020年度) 特別  - その他

  • クラウンによる咬合再建学 (2020年度) 第2学期  - 水4

  • デジタル技術と口腔インプラントによる咬合再建手技実習 (2020年度) 第1学期  - 金5,金6,金7

  • ブリッジによる咬合再建学 (2020年度) 第3学期  - 水1

  • ブリッジによる咬合再建手技実習 (2020年度) 第3学期  - 月5,月6,月7

  • 口腔インプラント義歯学(実習(臨床実習)) (2020年度) 特別  - その他

  • 口腔インプラント義歯学(講義・演習) (2020年度) 特別  - その他

  • 口腔リハビリテーション学(実習(臨床実習)) (2020年度) 特別  - その他

  • 口腔リハビリテーション学(講義・演習) (2020年度) 特別  - その他

  • 固定性補綴装置による咬合再建手技実習 (2020年度) 第4学期  - 月5,月6,月7

  • 接着の科学と咬合再建手技実習 (2020年度) 第2学期  - 火6,火7,火8

  • 顎関節症・口腔顔面痛治療学(実習(臨床実習)) (2020年度) 特別  - その他

  • 顎関節症・口腔顔面痛治療学(講義・演習) (2020年度) 特別  - その他

  • 高度補綴治療学(実習(臨床実習)) (2020年度) 特別  - その他

  • 高度補綴治療学(講義・演習) (2020年度) 特別  - その他

▼全件表示