Trinh Nhu Thuy, Yamashita Toshiharu, Tu Tran Cam, Kato Toshiki, Ohneda Kinuko, Sato Fujio, Ohneda Osamu
Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.
Laboratory of Molecular Pathophysiology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki 370-0033, Japan.
Biochem Biophys Res Commun. 2016 May 13;473(4):1111-1118. doi: 10.1016/j.bbrc.2016.04.025. Epub 2016 Apr 7.
Microvesicles (MVs) derived from mesenchymal stem cells showed the ability to alter the cell phenotype and function. We previously demonstrated that type 2 diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) increase in cell aggregation and adhesion in vitro and impair wound healing in vivo. However, the characterization and function of MVs derived from human non-diabetic AT-MSCs (nAT-MSCs) remain unknown. In this study, we characterized nAT-MSC-derived MVs and their function after the transfection of dAT-MSCs with MVs using the scratch assay and a flap mouse model. We found that human nAT-MSC-derived MVs expressed MSC-surface markers and improved dAT-MSC functions by altering the expression of genes associated with cell migration, survival, inflammation, and angiogenesis as well as miR29c and miR150. Remarkably, the transfection of dAT-MSCs with nAT-MSC-derived MVs improved their migration ability in vitro and wound healing ability in a flap mouse model. These results demonstrate a promising opportunity to modify the function of dAT-MSCs for therapeutic stem cell application in diabetic patients.
源自间充质干细胞的微泡(MVs)显示出改变细胞表型和功能的能力。我们之前证明,2型糖尿病脂肪组织来源的间充质干细胞(dAT-MSCs)在体外细胞聚集和黏附增加,在体内损害伤口愈合。然而,源自人非糖尿病脂肪组织间充质干细胞(nAT-MSCs)的MVs的特性和功能仍不清楚。在本研究中,我们使用划痕试验和皮瓣小鼠模型,对nAT-MSC来源的MVs及其在用MVs转染dAT-MSCs后的功能进行了表征。我们发现,人nAT-MSC来源的MVs表达间充质干细胞表面标志物,并通过改变与细胞迁移、存活、炎症和血管生成以及miR29c和miR150相关的基因表达来改善dAT-MSC的功能。值得注意的是,用nAT-MSC来源的MVs转染dAT-MSCs可提高其在体外的迁移能力和在皮瓣小鼠模型中的伤口愈合能力。这些结果表明,在糖尿病患者中修饰dAT-MSCs的功能以用于治疗性干细胞应用具有广阔前景。
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