Exosomes from Adipose-Derived Stem Cells (ADSCs) Overexpressing miR-21 Promote Vascularization of Endothelial Cells

被引:108
作者
An, Yang [1 ]
Zhao, Jianfang [1 ]
Nie, Fangfei [1 ]
Qin, Zelian [1 ]
Xue, Hongyu [1 ]
Wang, Guanhuier [1 ]
Li, Dong [1 ]
机构
[1] Peking Univ, Dept Plast Surg, Hosp 3, 49 Huayuan North Rd, Beijing 100191, Peoples R China
关键词
INDUCIBLE FACTOR-I; MICRORNAS; ANGIOGENESIS; INVASION; GROWTH; TISSUE; DIFFERENTIATION; PROLIFERATION; EXPRESSION; CANCER;
D O I
10.1038/s41598-019-49339-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In the past few years, exosomes released from adipose-derived stem cells (abbreviated as ADSCs) have shown promises to provide therapeutic benefits in the fields of regenerative medicine. miRNAs, existing in exosomes, are endogenous, small noncoding RNAs that play important roles in a variety of cellular functions and tumor development. Emerging evidences have indicated that miR-21 is one of the important miRNAs associated with tumor angiogenesis. In this study, we identified the role of exosomes from ADSCs overexpressing miR-21 in regulating/promoting vascularization of endothelial cells. Experimental data indicated an elevated miR-21 level in exosomes released by ADSCs overexpressing miR-21. In vitro matrigel angiogenesis assay showed that exosomes secreted by ADSCs overexpressing miR-21 significantly promoted the vascularization of HUVEC cells (an endothelial cell line). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) revealed an upregulation of HIF-1 alpha, VEGF, SDF-1, p-Akt, p-ERK1/2 and downregulation of PTEN in response to miR-21 overexpression, indicating that miR-21 enriched exosomes induced angiogenesis through Akt and ERK activation and also HIF-1 alpha and SDF-1 expression. Our work suggests that exosomes from ADSCs that overexpressing miR-21 can potentially promote vascularization and therefore the transplantation of exosomes from their culture may be suitable for clinical effort in regenerative medicine.
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页数:10
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