Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31.
Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31.
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DOI：
10.5966/sctm.2015-0177
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发表时间：
2016-04
影响因子：
6
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Kang T;Jones TM;Naddell C;Bacanamwo M;Calvert JW;Thompson WE;Bond VC;Chen YE;Liu D
探讨了干细胞释放的微泡（MV）在促血管生成治疗中的潜在作用。从脂肪来源的干细胞（ASCs）中释放MV，并能够增加人脐静脉内皮细胞的迁移和管形成。发现来自ASC的MV，特别是来自内皮分化培养基预处理的ASC的MV具有升高的microRNA-31水平并促进血管生成。细胞分泌是基于干细胞的治疗性血管生成的重要机制，沿着细胞分化为血管内皮细胞或平滑肌细胞。细胞释放的微泡（MV）最近被认为在细胞间通讯中发挥着重要作用。本研究的目的是探索干细胞释放的MV在促血管生成治疗中的潜在作用。我们首次观察到，MV从脂肪来源的干细胞（ASCs）中释放出来，并能够增加人脐静脉内皮细胞（HUVECs）的迁移和管形成。内皮细胞分化液预处理可促进平滑肌细胞释放微血管，增强微血管的促血管生成作用。RNA分析显示，microRNA在ASC释放的MV中富集，并且MV中的microRNA-31（miR-31）水平在MV供体ASC的EDM预处理后显著升高。进一步的研究表明，MVs中的miR-31有助于HUVECs的迁移和管形成，小鼠主动脉环的微血管生长，以及小鼠Matrigel栓的血管形成。此外，抑制因子HIF-1，一种抗血管生成基因，被确定为HUVEC中miR-31的靶点。我们的研究结果提供了第一个证据，即来自ASC的MV，特别是来自EDM预处理的ASC的MV，促进血管生成，并且miR-31的递送可能有助于促血管生成作用。这项研究提供的证据表明，微泡（MV）从脂肪来源的干细胞（ASC），特别是从内皮分化培养基（EDM）预处理的ASC，促进血管生成。促血管生成的一个潜在机制可能是microRNA-31通过MV从ASC递送到血管内皮细胞，其中抑制因子HIF-1被靶向和抑制。研究结果揭示了MV在介导ASC诱导的血管生成中的作用，并提出了一种潜在的基于MV的缺血性疾病血管生成治疗方法。
The potential effects of stem cell-released microvesicles (MVs) in proangiogenic therapy were explored. MVs were released from adipose-derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells. MVs from ASCs, particularly from endothelial differentiation medium-preconditioned ASCs, were found to have elevated levels of microRNA-31 and to promote angiogenesis. Cell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of this study was to explore the potential effects of stem cell-released MVs in proangiogenic therapy. We observed for the first time that MVs were released from adipose-derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the released MVs in vitro. RNA analysis revealed that microRNA was enriched in ASC-released MVs and that the level of microRNA-31 (miR-31) in MVs was notably elevated upon EDM-preconditioning of MV-donor ASCs. Further studies exhibited that miR-31 in MVs contributed to the migration and tube formation of HUVECs, microvessel outgrowth of mouse aortic rings, and vascular formation of mouse Matrigel plugs. Moreover, factor-inhibiting HIF-1, an antiangiogenic gene, was identified as the target of miR-31 in HUVECs. Our findings provide the first evidence that MVs from ASCs, particularly from EDM-preconditioned ASCs, promote angiogenesis and the delivery of miR-31 may contribute the proangiogenic effect. This study provides the evidence that microvesicles (MVs) from adipose-derived stem cells (ASCs), particularly from endothelial differentiation medium (EDM)-preconditioned ASCs, promote angiogenesis. An underlying mechanism of the proangiogenesis may be the delivery of microRNA-31 via MVs from ASCs to vascular endothelial cells in which factor-inhibiting HIF-1 is targeted and suppressed. The study findings reveal the role of MVs in mediating ASC-induced angiogenesis and suggest a potential MV-based angiogenic therapy for ischemic diseases.