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

机译:来自脂肪干细胞(ADSCs)的exosomes过度表达miR-21促进内皮细胞的血管化。

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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-1α, 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-1α 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.
机译:在过去的几年中,从脂肪干细胞(缩写为ADSCs)释放的外泌体显示出有望在再生医学领域提供治疗益处。存在于外来体中的miRNA是内源性小非编码RNA,在各种细胞功能和肿瘤发展中起重要作用。新兴证据表明,miR-21是与肿瘤血管生成相关的重要miRNA之一。在这项研究中,我们确定了过表达miR-21的ADSC的外泌体在调节/促进内皮细胞血管化中的作用。实验数据表明,过表达miR-21的ADSC释放的外泌体中miR-21的水平升高。体外基质胶血管生成试验表明,过表达miR-21的ADSC分泌的外泌体显着促进了HUVEC细胞(内皮细胞系)的血管形成。实时定量聚合酶链反应(qRT-PCR)和蛋白质印迹(WB)显示,miR-响应时,HIF-1α,VEGF,SDF-1,p-Akt,p-ERK1 / 2上调,而PTEN下调21过表达,表明富含miR-21的外泌体通过Akt和ERK激活以及HIF-1α和SDF-1表达诱导血管生成。我们的工作表明,过量表达miR-21的ADSC的外泌体可能促进血管生成,因此从其培养物中进行外泌体的移植可能适合再生医学的临床研究。

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