{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:41:23Z","timestamp":1791045683980,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T00:00:00Z","timestamp":1469491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In rats with type 1 diabetes (T1DM), the therapeutic effects and underlying mechanisms of action of stroke treatment were compared between bone-marrow stromal cells (BMSCs) derived from T1DM rats (DM-BMSCs) and BMSCs derived from normal rats (Nor-BMSCs). The novel role of microRNA-145 (miR-145) in mediating DM-BMSC treatment-induced benefits was also investigated. T1DM rats (n = 8 per group) underwent 2 hours of middle cerebral artery occlusion (MCAo) and were treated 24 hours later with the one of the following (5 \u00d7 106 cells administered i.v.): (a) phosphate-buffered saline (PBS); (b) Nor-BMSCs; (c) DM-BMSCs; (d) DM-BMSCs with miR-145 overexpression (miR-145+\/+DM-BMSCs); or (e) Nor-BMSCs with miR-145 knockdown. Evaluation of functional outcome, vascular and white-matter remodeling and microRNA expression was made, and in vitro studies were performed. In vitro, DM-BMSCs exhibited decreased miR-145 expression and increased survival compared with Nor-BMSCs. Capillary tube formation and axonal outgrowth in cultured primary cortical neurons were significantly increased by DM-BMSC-conditioned medium compared with Nor-BMSCs, and significantly decreased by miR-145+\/+DM-BMSC-conditioned medium compared with DM-BMSCs. In T1DM rats in which stroke had been induced (T1DM stroke rats), DM-BMSC treatment significantly improved functional outcome, increased vascular and white matter remodeling, decreased serum miR-145 expression, and increased expression of the miR-145 target genes adenosine triphosphate-binding cassette transporter 1 (ABCA1) and insulin-like growth factor 1 receptor (IGFR1), compared with Nor-BMSCs or PBS treatment. However, miR-145+\/+DM-BMSCs significantly increased serum miR-145 expression and decreased brain ABCA1 and IGFR1 expression, as well as attenuated DM-BMSC-induced neurorestorative effects in T1DM-MCAo rats. DM-BMSCs exhibited decreased miR-145 expression. In T1DM-MCAo rats, DM-BMSC treatment improved functional outcome and promoted neurorestorative effects. The miR-145\/ABCA1\/IGFR1 pathway may contribute to the enhanced DM-BMSCs\u2019 functional and neurorestorative effects in T1DM stroke rats.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In rats with type 1 diabetes (T1DM), the therapeutic effects and underlying mechanisms of action of stroke treatment were compared between bone-marrow stromal cells (BMSCs) derived from T1DM rats (DM-BMSCs) and BMSCs derived from normal rats (Nor-BMSCs). In vitro, DM-BMSCs and derived exosomes decreased miR-145 expression and increased DM-BMSC survival, capillary tube formation, and axonal outgrowth, compared with Nor-BMSCs; these effects were decreased by DM-BMSCs in which miR-145 was overexpressed. In vivo, compared with Nor-BMSC or phosphate-buffered saline treatment, DM-BMSC treatment improved functional outcome and vascular and white matter remodeling, decreased serum miR-145 expression, and increased expression of the miR-145 target genes ABCA1 and IGFR1. microRNA-145 mediated the benefits induced by DM-BMSC treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5966\/sctm.2015-0349","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T22:14:08Z","timestamp":1469571248000},"page":"1656-1667","source":"Crossref","is-referenced-by-count":65,"title":["miR-145 Regulates Diabetes-Bone Marrow Stromal Cell-Induced Neurorestorative Effects in Diabetes Stroke Rats"],"prefix":"10.1093","volume":"5","author":[{"given":"Chengcheng","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, People\u2019s Republic of China"},{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchun","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chopp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"},{"name":"Department of Physics, Oakland University, Rochester, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima","family":"Venkat","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"},{"name":"Department of Physics, Oakland University, Rochester, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Zacharek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhou","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyun","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated 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