Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31 Adipose-Derived Stem Cells Induce Angiogenesis via Microvesicle Transport of miRNA-31

• Type of Material: Article
• Authors: Ting Kang, Nanchang University; Tia M. Jones, Morehouse School of Medicine; Clayton Naddell, Morehouse School of Medicine; Methode Bacanamwo, Morehouse School of Medicine; John Calvert, Emory University; Winston E. Thompson, Morehouse School of Medicine; Vincent C. Bond, Morehouse School of Medicine; Y. Eugene Chen, University of Michigan; Dong Liu, Morehouse School of Medicine
• Language: English
• Date: 2016-04-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © AlphaMed Press 2016.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.5966/sctm.2015-0177
• Title of Journal or Parent Work: Stem Cells Translational Medicine
• Volume: 5
• Issue: 4
• Start Page: 440
• End Page: 450
• Grant/Funding Information: This work was supported, in whole or in part, by NIH Grants SC2GM099629 and G12RR003034 to D.L.
• Keywords: Life Sciences & Biomedicine; Science & Technology; OXIDATIVE STRESS; miRNA; Angiogenesis; Cell & Tissue Engineering; ENDOTHELIAL PROGENITOR CELLS; Microvesicle; MYOCARDIAL-INFARCTION; Cell Biology; HORIZONTAL TRANSFER; GENE-THERAPY; Endothelial cell; Adipose stem cell; MESSENGER-RNA; IN-VITRO; EXTRACELLULAR VESICLES; ISCHEMIC-HEART-DISEASE
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery

Abstract

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-releasedMVsin 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 ofhuman umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the releasedMVsin vitro. RNAanalysis 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.