Comprehensive development of next-generation direct reprogramming method applicable to treatment for various neurological diseases

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10827
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Okayama University
• Principal Investigator: Yamashita Toru 岡山大学, 医歯薬学総合研究科, 講師 (60644408)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脳梗塞 / iN細胞 / ダイレクトリプログラミング

Outline of Final Research Achievements

In this study, we conducted experiments to express Ascl1, Sox2, and NeuroD1 in glial cells in the post-stroke brain of mice using retrovirus. As a result, it was revealed that neural progenitor cells were induced 24 days after the retrovirus injection and mature neurons were induced 52 days. These results suggested that nerve cells can be reproduced from the abundant remaining glial cells in the brain. In the future, we will further improve the induction efficiency, establish safety and promote the development of treatment methods that contribute to the improvement of motor paralysis in patients with ischemic stroke.

Free Research Field

脳梗塞、再生治療、神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

今回、神経特異的転写因子であるAscl1やSox2、NeuroD1を脳内グリア細胞に強制発現させることで、神経系細胞に直接的に誘導することができ、脳梗塞で一旦失われてしまった神経細胞も、周囲に豊富に残っているグリア細胞から誘導し補充できる可能性が示すことが出来た。今後3つの転写因子を発現できる高力価ポリシストロニックベクター等を用いるなど、誘導効率を更に向上させると共に安全性を確立し、脳梗塞患者の運動麻痺改善に寄与する治療法開発を進めていく。