Development and application of human neuromuscular junctions

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05352
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: Saito Megumu 京都大学, iPS細胞研究所, 准教授 (90535486)
• Co-Investigator(Kenkyū-buntansha): 吉田 路子 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70754571)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 多能性幹細胞 / 神経筋接合部

Outline of Final Research Achievements

In this study, we constructed a pluripotent-cell based system that simultaneously induces neuromuscular junctions (NMJs) which contain motor neurons, skeletal muscle, and Schwann cells (Lin CY, JCI insight 2019, patent pending). We also showed that spinal muscular atrophy can be used as a prototype for model construction and analysis of NMJ lesions in this system. In the future, we plan to use this unique system to analyze congenital myasthenic syndrome for which no specific treatment exists and spinal muscular atrophy for which the functional analysis of the disease-causing molecule has not been sufficiently advanced.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

今回開発した分化系は機能的なNMJを誘導することができ、形態的あるいは細胞生物学的にNMJの発達を模倣することができることから、疾患モデリングに非常に有用であると考えられる。近年、神経筋疾患の多くが神経筋接合部の異常を伴うことが見いだされつつある。今回の成果は、従来は不可能であったヒトNMJ疾患の病態解析をin vitroでヒトの細胞を用い研究を可能にし、これらの疾患の病態解明や治療法開発に貢献することができる。