Department of Plastic Surgery, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, China.
Sci Rep. 2019 Sep 6;9(1):12861. doi: 10.1038/s41598-019-49339-y.
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.
在过去的几年中，脂肪来源干细胞（简称 ADSCs）释放的外泌体在再生医学领域显示出提供治疗益处的潜力。存在于外泌体中的 miRNA 是内源性的、小的非编码 RNA，在多种细胞功能和肿瘤发展中发挥重要作用。新出现的证据表明，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 来源的外泌体在调节/促进内皮细胞血管生成中的作用。实验数据表明，过表达 miR-21 的 ADSC 释放的外泌体中 miR-21 水平升高。体外基质胶血管生成实验表明，过表达 miR-21 的 ADSC 分泌的外泌体显著促进了 HUVEC 细胞（一种内皮细胞系）的血管生成。定量实时聚合酶链反应（qRT-PCR）和 Western blot（WB）显示，HIF-1α、VEGF、SDF-1、p-Akt、p-ERK1/2 的表达上调和 PTEN 的下调对 miR-21 的过表达有反应，表明富含 miR-21 的外泌体通过 Akt 和 ERK 激活以及 HIF-1α 和 SDF-1 的表达诱导血管生成。我们的工作表明，过表达 miR-21 的 ADSC 来源的外泌体可以潜在地促进血管生成，因此，其培养物中外泌体的移植可能适合再生医学中的临床努力。
