脐带血干细胞通过分泌富含miR-126外泌体治疗2型糖尿病小鼠脑卒中

Diabetes mellitus (DM) instigates a cascade of events leading to vascular endothelial cells dysfunction and decrease of miR-126 level, increases risk of experiencing ischemic stroke, develops more white matter damage and leads to a worse prognosis than non-DM patients. miR-126 facilitates angiogenesis, regulates endothelial cells function and promotes axonal outgrowth. Our preliminary data show that human umbilical cord blood cells (HUCBCs), releases exosomes containing miR-126 increases brain endothelial cells (BECs) miR-126 expression; manipulation of BECs or HUCBCs miR-126 modulates Angiopoietin1 (Ang1) expression level; Ang1 increases primary cortical neurons axonal outgrowth and increases oligodendrocytes survival and differentiation. HUCBCs treatment of stroke in type 2 diabetic (T2DM) mice significantly improves functional outcome. We propose that HUCBCs release miR-126 enriched exosomes to increase BECs miR-126 expression then upregulate Angiopoietin1 expression. The increasing of miR-126/Ang1 signaling pathway by HUCBCs treatment promotes vascular and white matter remodeling, thereby improves functional outcome after extraluminal distal middle cerebral artery occlusion (dMCAo) stroke in T2DM mice. Our studies will provide fundamental insights into neurorestorative therapy on stroke in DM populations and a fresh approach for studies on stroke with comorbidities.

糖尿病(DM)造成血管内皮功能障碍，降低体内miR-126表达水平，增加脑卒中的发病率，加重脑白质损伤导致脑卒中预后不良。miR-126可以易化新血管生成、调节血管内皮细胞功能并促进轴索生长。前期研究表明，脐带血干细胞（HUCBCs）及其分泌的外泌体富含miR-126，可促进脑内皮细胞（BECs）miR-126和Angiopoietin1（Ang1）的表达水平；Ang1诱导原代皮层神经元轴索生长，增加少突胶质细胞存活和分化；HUCBCs改善糖尿病脑卒中神经功能恢复。我们设想，HUCBCs治疗T2DM脑卒中，通过释放富含miR-126的外泌体上调BECs中miR-126的表达，进而调节Ang1表达促进血管和脑白质重塑，改善神经功能恢复。本研究探讨HUCBCs 治疗糖尿病脑卒中的作用机制并为糖尿病脑卒中神经功能恢复治疗研究奠定基础，也对合并其他疾病的脑卒中研究提供理论依据和借鉴。

糖尿病(DM)造成血管内皮功能障碍，降低体内miR-126表达水平，增加脑卒中的发病率，加重脑白质损伤导致脑卒中预后不良。miR-126可以易化新血管生成、调节血管内皮细胞功能并促进轴索生长。前期研究表明，脐带血干细胞（HUCBCs）及其分泌的外泌体富含miR-126，可促进脑内皮细胞（BECs）miR-126和Angiopoietin1（Ang1）的表达水平；Ang1诱导原代皮层神经元轴索生长，增加少突胶质细胞存活和分化；HUCBCs改善糖尿病脑卒中神经功能恢复。我们的研究发现，HUCBCs治疗T2DM脑卒中，通过释放富含miR-126的外泌体上调BECs中miR-126的表达，进而调节Ang1表达促进血管和脑白质重塑，改善神经功能恢复。本研究HUCBCs 治疗糖尿病脑卒中的作用机制并为糖尿病脑卒中神经功能恢复治疗研究奠定基础，也对合并其他疾病的脑卒中研究提供理论依据和借鉴。