{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:02:12Z","timestamp":1793041332642,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda Science Foundation","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"Grant-in-Aid for Graduate Students","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"Hyogo Medical University","award":["2022"],"award-info":[{"award-number":["2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We previously demonstrated that neural stem\/progenitor cells (NSPCs) were induced within and around the ischemic areas in a mouse model of ischemic stroke. These injury\/ischemia-induced NSPCs (iNSPCs) differentiated to electrophysiologically functional neurons in vitro, indicating the presence of a self-repair system following injury. However, during the healing process after stroke, ischemic areas were gradually occupied by inflammatory cells, mainly microglial cells\/macrophages (MGs\/M\u03a6s), and neurogenesis rarely occurred within and around the ischemic areas. Therefore, to achieve neural regeneration by utilizing endogenous iNSPCs, regulation of MGs\/M\u03a6s after an ischemic stroke might be necessary. To test this hypothesis, we used iNSPCs isolated from the ischemic areas after a stroke in our mouse model to investigate the role of MGs\/M\u03a6s in iNSPC regulation. In coculture experiments, we show that the presence of MGs\/M\u03a6s significantly reduces not only the proliferation but also the differentiation of iNSPCs toward neuronal cells, thereby preventing neurogenesis. These effects, however, are mitigated by MG\/M\u03a6 depletion using clodronate encapsulated in liposomes. Additionally, gene ontology analysis reveals that proliferation and neuronal differentiation are negatively regulated in iNSPCs cocultured with MGs\/M\u03a6s. These results indicate that MGs\/M\u03a6s negatively impact neurogenesis via iNSPCs, suggesting that the regulation of MGs\/M\u03a6s is essential to achieve iNSPC-based neural regeneration following an ischemic stroke.<\/jats:p>","DOI":"10.3390\/cells12162040","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:24:47Z","timestamp":1691663087000},"page":"2040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Microglia Negatively Regulate the Proliferation and Neuronal Differentiation of Neural Stem\/Progenitor Cells Isolated from Poststroke Mouse Brains"],"prefix":"10.3390","volume":"12","author":[{"given":"Yoshinobu","family":"Hirano","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya 663-8501, 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, 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"}]},{"given":"Akiko","family":"Nakano-Doi","sequence":"additional","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University, 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\/0000-0001-7384-4835","authenticated-orcid":false,"given":"Shuji","family":"Kubo","sequence":"additional","affiliation":[{"name":"Institute for Advanced Medical Sciences, Hyogo Medical University, 1-1 Mukogawacho, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Minato","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, 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"}]},{"given":"Masafumi","family":"Sakagami","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-2485","authenticated-orcid":false,"given":"Kenzo","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head & Neck Surgery, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya 663-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.3390\/cells9061374","article-title":"Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even after Lethal Ischemia with Mature Neural Cell Death","volume":"9","author":"Tanaka","year":"2020","journal-title":"Cells"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12997","DOI":"10.3390\/ijms222312997","article-title":"Establishment of a Reproducible Ischemic Stroke Model in Nestin-GFP Mice with High Survival Rates","volume":"22","author":"Nishie","year":"2021","journal-title":"Int. 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