application of induced mesenchymal stem cells from human iPS cells to cell therapy in muscular dystrophy
| Project/Area Number |
16K08725
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Suzuki Yuko 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 室長 (00342931)
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| Co-Investigator(Kenkyū-buntansha) |
武田 伸一 国立研究開発法人国立精神・神経医療研究センター, その他部局等, 部長 (90171644)
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| Research Collaborator |
Takemura Fusako
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 間葉系幹細胞 / 筋ジストロフィー / 再生 / 移植治療 / 筋前駆細胞 / 骨格筋 / 分化 / ヒトiPS細胞 / 移植 / 筋再生 / 細胞移植 / 多能性幹細胞 / 骨格筋前駆細胞 / 人工多能性幹細胞 / 再生医療 |
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| Outline of Final Research Achievements |
Mesenchymal stem cells (MSCs) may improve the efficiency of transplantation of myogenic cells into dystrophic muscle, because they have anti-inflammatory and immunomodulatory properties, protect cells from apoptosis, and secrete factors which support muscle growth. We induced MSCs (iMSC) from hiPSCs. FACS revealed that iMSC express MSC markers, CD73, CD90 and CD105. iMSC could be induced to differentiate into osteogenic, chondrogenic, and adipogenic cells.iMSCs showed higher proliferative potential than human bone marrow-derived MSCs (BM-MSC). Both MSCs promoted the differentiation of human myoblasts, when co-cultured by using the transwell, suggesting that MSCs secrete soluble factors which promote muscle differentiation. Unexpectedly, co-transplantation of iMSC with hiPSC-derived myogenic cells into immuno-deficient DMD model mice did not produce dystrophin-positive myofibers. The factors which inhibit differentiation of hiPSC-derived myogenic cells in vivo remain to be clarified.
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| Academic Significance and Societal Importance of the Research Achievements |
筋ジストロフィーにおいては骨格筋線維が変性・壊死し、それを再生する組織幹細胞である筋衛星細胞の機能も病気の進行に伴い低下してくる。その一因として、骨格筋の間葉系前駆細胞の機能の低下があると言われている。我々はヒトiPS細胞から誘導した間葉系前駆細胞がヒト多能性幹細胞（iPS細胞）から誘導した筋前駆細胞の筋分化をin vitroにおいて促進することを明らかにした。今後は共移植に用いることで、その治療用細胞としての有用性と安全性を示すとともに、骨格筋の恒常性維持及び筋ジストロフィーの分子病態における間葉系前駆細胞の機能も明らかにしていく予定である。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Induction of pluripotent stem cells from a manifesting carrier of Duchenne muscular dystrophy and characterization of their X-inactivation status2017
Author(s)
Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu ichi Goto, Shin’ichi Takeda
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Journal Title
Stem Cells International
Volume: 2017
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cell-surface protein profiling identifies distinctive markers of progenitor cells in human skeletal muscle.2016
Author(s)
Uezumi A, Nakatani M, Ikemoto-Uezumi M, Yamamoto N, Morita M, Yamaguchi A, Yamada H, Kasai T, Masuda S, Narita A, Miyagoe-Suzuki Y, Takeda S, Fukada S, Nishino I, Tsuchida K.
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Journal Title
Stem Cell Report
Volume: 7
Pages: 263-278
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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