Analysis of induced iNSPCs within the ischemic area and neural regeneration mechanism using transgenic mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16934
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Doi Akiko 兵庫医科大学, 医学部, 助教 (70793321)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳梗塞 / 脳傷害誘導性神経幹細胞

Outline of Final Research Achievements

Accumulating evidence reveals that endogenous neural stem/progenitor cells (NSPCs) are activated under pathological conditions, such as stroke. To elucidate the localization of these cells, researchers have created genetically modified mice wherein the neural stem cell marker, Nestin, is labeled with a green fluorescent protein (Nestin-GFP mice).
Immunohistochemical analysis of Nestin-GFP (CB-17 line) mice revealed that GFP was expressed not only in the subventricular zone (SVZ), a well-known neurogenic region of the brain, but also in the infarct region. Neurospheres, a hallmark of NSPCs, were formed from both tissues after the isolation and culture of the SVZ and infarcted regions, respectively. They differentiated into various neural lineages, including neuronal cells, astrocytes, and oligodendrocytes. However, PCR analysis revealed that NSPCs from the SVZ and infarcted region had distinct characteristics, implying that these cells have a distinct origin.

Free Research Field

病態神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究においては脳梗塞巣内に生じるiNSPCsは成体脳にもともと存在するSVZ由来神経幹細胞と異なる起源や特性を持つことが示唆された。iNSPCs元来壊死巣と呼ばれていた組織由来であり、そこから発生する細胞のトレースに成功した。また、本研究により樹立したNestin-GFP組換えマウス（CB-17 系統）は、再現性や生存率が高いことから、脳梗塞病態時において、神経幹細胞を起点とした組織修復及び神経再生機構の解明や評価に極めて有用なツールとなり得ると考えられる。