Glial cell-derived exosomes as a new treatment in the chronic phase after stroke

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17020
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Juntendo University
• Principal Investigator: Hira Kenichiro 順天堂大学, 医学部, 助教 (60821725)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エクソソーム / 脳梗塞慢性期 / 軸索再生 / アストロサイト

Outline of Final Research Achievements

The mechanisms of functional recovery treated with glial cell-derived exosomes in the chronic phase after stroke were not elucidated. Therefore, we focused on serum-derived exosomes circulating in the blood. The amount of protein was increased in the 28-day-exo group compared with the Pre-exo group. In primary cultured neurons, 28-day-exo treated neurons had significantly elongated axons compared to the OGD group. In primary cultured astrocytes, S100A10 positive cells increased and C3d positive astrocytes decreased in 28-day-exo treated group compared to the OGD group. In animal models, neurological manifestation and motor function were significantly improved in the 28-day-exo group compared with the vehicles. Serum-derived exosomes may be a novel treatment to promote recovery during the chronic phase after stroke.

Free Research Field

脳卒中

Academic Significance and Societal Importance of the Research Achievements

エクソソームはmiRNAなどの情報を含有する細胞間伝達分子として各疾患治療に応用されているが、効果実証は近距離における限定的なものである。しかし、エクソソーム内でmiRNAは安定していることから、遠距離をターゲットとした治療法の開発が実現可能と考えた。さらに、単一細胞由来のエクソソームによる直接的な機能回復効果のみならず、循環するエクソソームを介した全身の諸臓器との相互作用に着目するという点でより実臨床に近い形で最大限の機能改善効果が期待できると考えた。本研究では、エクソソームの経静脈的投与による脳梗塞後慢性期機能回復効果の実証により遠距離をターゲットとした治療法の開発に近づいたと言える。