Nakagomi Takayuki
Institute for Advanced Medical Sciences, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
Stem Cells. 2025 May 27;43(6). doi: 10.1093/stmcls/sxaf015.
In the past, the mammal central nervous system (CNS) was assumed to lack the capacity for neural repair. However, increasing evidence shows that the CNS has repair capacity after injury. The migratory capacity of neural stem/progenitor cells (NSPCs) from subventricular zones (SVZ) is limited, and the precise repair mechanism active after ischemic stroke remains unknown. Consequently, it remains unclear how neural regeneration occurs in regions far from the SVZ, such as the cortex, especially given that these NSPCs can only migrate toward ischemic areas within specific brain regions. Nonetheless, using a mouse model of ischemic stroke with ischemic areas limited to the ipsilateral side of the cortex, we previously identified regionally-derived stem cells, injury/ischemia-induced stem cells (iSCs), within poststroke areas. Moreover, we showed that iSCs, which had the potential to differentiate into electrophysiologically functional neurons, were present within ischemic areas in poststroke human brains. This indicates that ischemic insult can activate locally-derived stem cells, even in nonneurogenic zones, and that iSCs can help achieve neural regeneration after ischemic stroke. However, inflammatory cells typically fill ischemic areas impairing neural regeneration in these areas. Here, we present the origin, characterization, and roles of iSCs based on our recent research. In addition, we discussed the potential of iSC-based therapies to achieve neural regeneration after ischemic stroke.
过去，人们认为哺乳动物的中枢神经系统（CNS）缺乏神经修复能力。然而，越来越多的证据表明，中枢神经系统在受伤后具有修复能力。来自脑室下区（SVZ）的神经干细胞/祖细胞（NSPCs）的迁移能力有限，缺血性中风后激活的精确修复机制仍然未知。因此，目前尚不清楚在远离脑室下区的区域，如皮质，神经再生是如何发生的，特别是考虑到这些神经干细胞/祖细胞只能向特定脑区内的缺血区域迁移。尽管如此，我们之前使用了一种缺血性中风小鼠模型，其缺血区域仅限于皮质的同侧，我们在中风后区域内鉴定出了区域来源的干细胞，即损伤/缺血诱导干细胞（iSCs）。此外，我们还表明，具有分化为电生理功能神经元潜力的iSCs存在于中风后人类大脑的缺血区域。这表明，即使在非神经源性区域，缺血性损伤也能激活局部来源的干细胞，并且iSCs有助于在缺血性中风后实现神经再生。然而，炎症细胞通常会填充缺血区域，损害这些区域的神经再生。在此，我们根据最近的研究介绍了iSCs的起源、特征和作用。此外，我们还讨论了基于iSCs的疗法在缺血性中风后实现神经再生的潜力。
