Establishment of a skeletal muscle cell model of myotonic dystrophy type 1 using urine derived cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15621
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Shinshu University
• Principal Investigator: Sato Mitsuto 信州大学, 医学部, 特任助教 (10816630)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 尿中細胞 / 筋強直性ジストロフィー / 細胞モデル

Outline of Final Research Achievements

Urinary derived cells(UDCs) isolated and cultured from DM1 patients showed formation of nuclear RNA aggregates (RNA foci), co-localization of RNA foci and MBNL1, and CTG repeat elongation with passaging, reflecting DM1 pathology. siRNAs targeting the DMPK gene reduced RNA foci, indicating that UDCs showed the potential to be used as a cellular model for therapeutic development. The diverse population of UDCs hindered the induction of muscle differentiation, and the desired DM1 skeletal muscle cell model could not be established within the time frame of this study. However, we were able to show that UDCs reflect the pathology of individual patients and are a useful tool that can contribute to the development of personalized medicine.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究期間内では目的としたDM1骨格筋細胞モデルの構築には至らなかったが、DM1患者由来の尿中細胞は病態の根本的原因である核内RNA凝集体の形成、継代に伴うCTGリピート伸長を呈しており、患者病態を反映したバイオマーカーとしてのポテンシャルを示すことができた。尿中細胞は個々の患者の病態に応じた個別化医療の開発に寄与する有用なツールであることを提示することができたと考える。