Analysis of molecular mechanisms regulating stemness in muscle stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Hayashi Shinichiro 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 疾病研究第一部, 室長 (10732381)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨格筋 / 筋幹細胞 / 筋ジストロフィー

Outline of Final Research Achievements

Satellite cells, a stem cell population in skeletal muscle, are essential for muscle regeneration. Transplanted satellite cells can fuse with endogenous muscle fibers and contribute regeneration in dystrophic muscle. However, once they are cultured in vitro, the ability of stemness maintenance is rapidly diminished. In this study, we aimed to understand molecular mechanisms to maintain stemness in satellite cells. We found that incubation of satellite cells with retinoic acid maintains satellite cell stemness and inhibits differentiation through retinoic acid receptor-alpha. In addition, laminin fragment also supports to inhibit satellite cell differentiation. This protocol improved engraftment of human satellite cells in dystrophic mice compared to conventional methods. Therefore, this new protocol may support ex vivo satellite cell expansion and stem cell therapy for treating dystrophy patients.

Free Research Field

筋幹細胞学

Academic Significance and Societal Importance of the Research Achievements

筋ジストロフィーの根治療法として骨格筋幹細胞である筋衛星細胞を移植する方法が挙げられるが、生体外で筋衛星細胞の未分化な状態を保持したまま培養することが難しく、移植に十分な数の筋衛星細胞を得られないことが課題となっている。本研究成果によって、これまでは困難であった骨格筋の幹細胞を生体外で未分化な状態のまま維持・増産できる事が可能となった。今後、レチノイン酸による筋分化抑制機構の分子メカニズムを明らかにすることによって細胞移植治療の発展に貢献できると期待される。