iPSCs modeling of blood brain barrier disruption in multiple sclerosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15711
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Nishihara Hideaki 山口大学, 大学院医学系研究科, 助教 (50780798)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 多発性硬化症 / iPS細胞 / 血液脳関門

Outline of Final Research Achievements

In multiple sclerosis (MS), the breakdown of the blood-brain barrier (BBB) is implicated in the pathogenesis, but research progress has been hindered by the difficulty in accessing patient samples. This study demonstrated the direct involvement of BBB breakdown in MS pathogenesis by establishing patient-derived BBB models using induced pluripotent stem cells (iPSCs). Additionally, candidate molecules involved in BBB breakdown in MS were identified, and their functional analysis was conducted.

Free Research Field

臨床神経学

Academic Significance and Societal Importance of the Research Achievements

BBB破綻が直接的にMS病態に関わることを示した本研究成果は，これまでの免疫細胞を主体としてきたMSの病態理解とは全く別の，BBB破綻を中心とした病態解明，創薬標的の確立につながる．また，患者のBBBをin vitroに再現できることから，患者由来モデルはBBBを強固にする治療標的のスクリーニングとしての活用が期待される．BBBの破綻はMSのみならず，認知症をはじめとした数多くの神経疾患で共通して観察される現象であることから，その学術的・社会的意義は極めて大きい．