Unlocking the potential of regionally-activated injury/ischemia-induced stem cells for neural regeneration

Abstract 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 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.