{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:28:55Z","timestamp":1790908135467,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development (AMED)","award":["21nk0101538h0002"],"award-info":[{"award-number":["21nk0101538h0002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Increasing evidence shows that the administration of mesenchymal stem cells (MSCs) is a promising option for various brain diseases, including ischemic stroke. Studies have demonstrated that MSC transplantation after ischemic stroke provides beneficial effects, such as neural regeneration, partially by activating endogenous neural stem\/progenitor cells (NSPCs) in conventional neurogenic zones, such as the subventricular and subgranular zones. However, whether MSC transplantation regulates the fate of injury-induced NSPCs (iNSPCs) regionally activated at injured regions after ischemic stroke remains unclear. Therefore, mice were subjected to ischemic stroke, and mCherry-labeled human MSCs (h-MSCs) were transplanted around the injured sites of nestin\u2013GFP transgenic mice. Immunohistochemistry of brain sections revealed that many GFP+ cells were observed around the grafted sites rather than in the regions in the subventricular zone, suggesting that transplanted mCherry+ h-MSCs stimulated GFP+ locally activated endogenous iNSPCs. In support of these findings, coculture studies have shown that h-MSCs promoted the proliferation and neural differentiation of iNSPCs extracted from ischemic areas. Furthermore, pathway analysis and gene ontology analysis using microarray data showed that the expression patterns of various genes related to self-renewal, neural differentiation, and synapse formation were changed in iNSPCs cocultured with h-MSCs. We also transplanted h-MSCs (5.0 \u00d7 104 cells\/\u00b5L) transcranially into post-stroke mouse brains 6 weeks after middle cerebral artery occlusion. Compared with phosphate-buffered saline-injected controls, h-MSC transplantation displayed significantly improved neurological functions. These results suggest that h-MSC transplantation improves neurological function after ischemic stroke in part by regulating the fate of iNSPCs.<\/jats:p>","DOI":"10.3390\/cells13110939","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:19:46Z","timestamp":1717417186000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Administration of Human-Derived Mesenchymal Stem Cells Activates Locally Stimulated Endogenous Neural Progenitors and Reduces Neurological Dysfunction in Mice after Ischemic Stroke"],"prefix":"10.3390","volume":"13","author":[{"given":"Shuichi","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nakano-Doi","sequence":"additional","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"},{"name":"Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-2980","authenticated-orcid":false,"given":"Toshinori","family":"Sawano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu 525-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-4835","authenticated-orcid":false,"given":"Shuji","family":"Kubo","sequence":"additional","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Doe","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Hyogo Medical University (Kobe Campus), 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-410X","authenticated-orcid":false,"given":"Takayuki","family":"Nakagomi","sequence":"additional","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University (Nishinomiya Campus), 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"},{"name":"Department of Therapeutic Progress in Brain Diseases, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1161\/STROKEAHA.112.655621","article-title":"Intravenous thrombolysis and endovascular therapy for acute ischemic stroke with internal carotid artery occlusion: A systematic review of clinical outcomes","volume":"43","author":"Mokin","year":"2012","journal-title":"Stroke"},{"key":"ref_2","first-page":"880","article-title":"Thrombolytic therapy of acute ischemic stroke: Correlation of angiographic recanalization with clinical outcome","volume":"26","author":"Zaidat","year":"2005","journal-title":"AJNR Am. 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