{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T23:16:17Z","timestamp":1784848577338,"version":"3.55.0"},"reference-count":75,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T00:00:00Z","timestamp":1655510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","award":["94\u201003\u201087\u201030215"],"award-info":[{"award-number":["94\u201003\u201087\u201030215"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Regenerative medicine literature has demonstrated that the therapeutic potentials of mesenchymal stem cells (MSCs) in experimental stroke are attributed to secreted bioactive factors rather than to cell replacement. Here, we explored the effects of secretome or conditioned medium (CM) derived from human embryonic stem cell\u2010derived MSCs (hESC\u2010MSCs) on hippocampal neurogenesis, inflammation, and apoptosis in experimental stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ischemic stroke was induced by right middle cerebral artery occlusion (MCAO) in male Wistar rats, and CM was infused either one time (1\u2010h post\u2010stroke; CM1) or three times (1\u2010, 24\u2010, and 48\u2010h post\u2010stroke; CM3) into left lateral ventricle. Neurogenesis markers (Nestin, Ki67, Doublecortin, and Reelin) were assessed at transcript and protein levels in the dentate gyrus of the hippocampus on day seven following MCAO. In parallel, changes in the gene expression of markers of apoptosis (Bax and Bim, as well as an anti\u2010apoptotic marker of Bcl2), inflammation (IL\u20101\u03b2 and IL\u20106, as well as IL\u201010 as an anti\u2010inflammatory cytokine), trophic factors (BDNF, GDNF, NGF, and NT\u20103), and angiogenesis (CD31 and VEGF) in the hippocampus were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrate that CM3 treatment could stimulate neurogenesis and angiogenesis concomitant with inhibition of inflammation, apoptosis, and neuronal loss in ischemic brains. Furthermore, rats treated with CM3 exhibited upregulation in neurotrophic factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that hESC\u2010MSC\u2010CM could promote neurogenesis and protect brain tissue from ischemic injury, partly mediated by induction of angiogenesis and neurotrophic factors and inhibition of inflammatory and apoptotic factors expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13886","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T07:09:39Z","timestamp":1655536179000},"page":"1425-1438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Hippocampal neuroprotection mediated by secretome of human mesenchymal stem cells against experimental stroke"],"prefix":"10.1111","volume":"28","author":[{"given":"Afsaneh","family":"Asgari Taei","sequence":"first","affiliation":[{"name":"Neuroscience Research Center Shahid Beheshti University of Medical Sciences  Tehran Iran"},{"name":"Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Dargahi","sequence":"additional","affiliation":[{"name":"Neurobiology Research Center Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pariya","family":"Khodabakhsh","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Kadivar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Pasteur Institute of Iran  Tehran 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