Neo-angiogenesis induction by pluripotent stem cell Muse as a new therapeutic strategy for severer form of moyamoya disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: Miki Fujimura 東北大学, 医学系研究科, 非常勤講師 (00361098)
• Co-Investigator(Kenkyū-buntansha): 冨永 悌二 東北大学, 大学病院, 教授 (00217548) ; 新妻 邦泰 東北大学, 医工学研究科, 教授 (10643330) ; 坂田 洋之 東北大学, 医学系研究科, 非常勤講師 (80722305)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: もやもや病 / 血管新生 / 再生医療

Outline of Final Research Achievements

In the laboratory research, we established a reproducible chronic hypoperfusion model using mice and rat, and found significant neo-angiogenesis and the migration of immune cells to the brain surface after indirect pial synangiosis. Using moyamoya disease patients’ sample, we found increased serum levels of sCD163 (M2 macrophage-associated factor) and CXCL5, suggesting the contribution of intrinsic immune reaction in its pathophysiology （Fujimura et al. Brain Res 2018）. Finally, we found marked expression of endogenous pluripotent stem cells in the arachnoid membrane of moyamoya disease patients, indicating the possible role of endogenous stem cells in the intrinsic angiogenesis in moyamoya disease (Fujimura et al. submitted）.

Free Research Field

脳神経外科学、脳卒中学

Academic Significance and Societal Importance of the Research Achievements

厚労省指定難病で原因不明の脳血管障害であるもやもや病における、得意な免疫反応、遺伝子変異の病態に及ぼす影響について新たな知見が得られた。さらに患者クモ膜における内因性多能性幹細胞の発現上昇を見出し、本疾患特有の血管新生のメカニズムを解き明かし、重症例に対する血管新生療法の確立に新たな道を開いた。