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Because iSCs are stem cells induced under pathological conditions, such as ischemic stroke, the use of human brain-derived iSCs (h-iSCs) may represent a novel therapy for stroke patients. We performed a preclinical study by transplanting h-iSCs transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion (MCAO). Compared with PBS-treated controls, h-iSC transplantation significantly improved neurological function. To identify the underlying mechanism, green fluorescent protein (GFP)-labeled h-iSCs were transplanted into post-stroke mouse brains. Immunohistochemistry revealed that GFP+ h-iSCs survived around the ischemic areas and some differentiated into mature neuronal cells. To determine the effect on endogenous neural stem\/progenitor cells (NSPCs) by h-iSC transplantation, mCherry-labeled h-iSCs were administered to Nestin-GFP transgenic mice which were subjected to MCAO. As a result, many GFP+ NSPCs were observed around the injured sites compared with controls, indicating that mCherry+ h-iSCs activate GFP+ endogenous NSPCs. In support of these findings, coculture studies revealed that the presence of h-iSCs promotes the proliferation of endogenous NSPCs and increases neurogenesis. In addition, coculture experiments indicated neuronal network formation between h-iSC- and NSPC-derived neurons. These results suggest that h-iSCs exert positive effects on neural regeneration through not only neural replacement by grafted cells but also neurogenesis by activated endogenous NSPCs. Thus, h-iSCs have the potential to be a novel source of cell therapy for stroke patients.<\/jats:p>","DOI":"10.1093\/stcltm\/szad031","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T02:47:34Z","timestamp":1684896454000},"page":"400-414","source":"Crossref","is-referenced-by-count":14,"title":["Transplantation of Human Brain-Derived Ischemia-Induced Multipotent Stem Cells Ameliorates Neurological Dysfunction in Mice After Stroke"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-410X","authenticated-orcid":false,"given":"Takayuki","family":"Nakagomi","sequence":"first","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus) , Nishinomiya, Hyogo , Japan"},{"name":"Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University (Nishinomiya Campus) , Nishinomiya, Hyogo , 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