Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential.
Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential.
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DOI：
10.1186/1478-811x-12-26
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发表时间：
2014-04-11
期刊：
影响因子：
--
通讯作者：
Camussi G
中科院分区：
文献类型：
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作者：
Lopatina T;Bruno S;Tetta C;Kalinina N;Porta M;Camussi G
一些研究证明了脂肪间充质干细胞（ASC）在血管生成中的作用。血管生成的机制被归因于旁分泌因子，因为这些细胞分泌大量的信号分子和生长因子。最近已经表明，除了可溶性因子之外，包括外泌体和微泡的细胞外囊泡（EV）可能在细胞间通讯中起主要作用。已经表明EV涉及血管生成过程。在此，我们研究了ASC释放的EV是否可以介导这些细胞的血管生成活性。我们的研究结果表明，ASC衍生的EV诱导人微血管内皮细胞（HMEC）体外血管样结构的形成。当在SCID小鼠中的Matrigel内皮下注射时，EV刺激的HMEC形成血管。用血小板衍生生长因子（PDGF）治疗ASCs可刺激EVs的分泌，改变其蛋白质组成并增强血管生成潜力。在基础条件下释放的EV的变化中，PDGF-EV携带c-kit和SCF，其在血管生成中发挥作用，因为特异性阻断抗体抑制体外血管样结构形成。PDGF-EV中基质金属蛋白酶含量的增加也可能是其血管生成活性的原因。我们的研究结果表明，由ASC释放的EV可能有助于ASC诱导的血管生成，并表明PDGF可能引发具有增强的血管生成潜力的EV的释放。
Several studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis. The angiogenic mechanism has been ascribed to paracrine factors since these cells secrete a plenty of signal molecules and growth factors. Recently it has been suggested that besides soluble factors, extracellular vesicles (EVs) that include exosomes and microvesicles may play a major role in cell-to-cell communication. It has been shown that EVs are implicated in the angiogenic process. Herein we studied whether EVs released by ASCs may mediate the angiogenic activity of these cells. Our results demonstrated that ASC-derived EVs induced in vitro vessel-like structure formation by human microvascular endothelial cells (HMEC). EV-stimulated HMEC when injected subcutaneously within Matrigel in SCID mice formed vessels. Treatment of ASCs with platelet-derived growth factor (PDGF) stimulated the secretion of EVs, changed their protein composition and enhanced the angiogenic potential. At variance of EVs released in basal conditions, PDGF-EVs carried c-kit and SCF that played a role in angiogenesis as specific blocking antibodies inhibited in vitro vessel-like structure formation. The enhanced content of matrix metalloproteinases in PDGF-EVs may also account for their angiogenic activity. Our findings indicate that EVs released by ASCs may contribute to the ASC-induced angiogenesis and suggest that PDGF may trigger the release of EVs with an enhanced angiogenic potential.