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We tested the neurorestorative effects of delayed human umbilical cord blood cell (HUCBC) treatment of stroke in type-2 diabetes (T2DM). db\/db-T2DM and db\/+-non-DM mice were subjected to distal middle cerebral artery occlusion (dMCAo) and were treated 3 days after dMCAo with: (a) non-DM\u2009+\u2009Phosphate buffered saline (PBS); (b) T2DM\u2009+\u2009PBS; (c) T2DM\u2009+\u2009na\u00efve-HUCBC; (d) T2DM\u2009+\u2009miR-126\u2212\/\u2212HUCBC. Functional evaluation, vascular and white-matter changes, neuroinflammation, and miR-126 effects were measured in vivo and in vitro. T2DM mice exhibited significantly decreased serum and brain tissue miR-126 expression compared with non-DM mice. T2DM+HUCBC mice exhibited increased miR-126 expression, increased tight junction protein expression, axon\/myelin, vascular density, and M2-macrophage polarization. However, decreased blood-brain barrier leakage, brain hemorrhage, and miR-126 targeted gene vascular cell adhesion molecule-1 and monocyte chemotactic protein 1 expression in the ischemic brain as well as improved functional outcome were present in HUCBC-treated T2DM mice compared with control T2DM mice. MiR-126\u2212\/\u2212HUCBC-treatment abolished the benefits of na\u00efve-HUCBC-treatment in T2DM stroke mice. In vitro, knock-in of miR-126 in primary cultured brain endothelial cells (BECs) or treatment of BECs with na\u00efve-HUCBCs significantly increased capillary-like tube formation, and increased axonal outgrowth in primary cultured cortical neurons; whereas treatment of BECs or cortical neurons with miR-126\u2212\/\u2212HUCBC attenuated HUCBC-treatment-induced capillary tube formation and axonal outgrowth. Our data suggest delayed HUCBC-treatment of stroke increases vascular\/white-matter remodeling and anti-inflammatory effects; MiR-126 may contribute to HUCBC-induced neurorestorative effects in T2DM mice.<\/jats:p>","DOI":"10.1002\/stem.2193","type":"journal-article","created":{"date-parts":[[2015,8,24]],"date-time":"2015-08-24T09:38:42Z","timestamp":1440409122000},"page":"102-113","source":"Crossref","is-referenced-by-count":58,"title":["MiR-126 Contributes to Human Umbilical Cord Blood Cell-Induced Neurorestorative Effects After Stroke in Type-2 Diabetic Mice"],"prefix":"10.1093","volume":"34","author":[{"given":"Jieli","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA"},{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, People's Republic of 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