Abstract 14211: Exosomes miR378a-3p Mediate Pro-angiogenic Activity of Human Adipose-derived Mesenchymal Stem Cells
Human adipose-derived mesenchymal cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interaction with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies found that functional miRNAs could be packaged into exosomes and transfered from donor cells into recipient cells, indicating transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether exosomes-derived miRNAs secreted by hADSCs were capable of influencing angiogenesis, a key step in tissue regeneration. For these purposes, we purified exosomes from hADSCs by ultracentrifugation and characterized their phenotype, followed by estimating their angiogenic potential in vitro. hADSCs secreted exosomes had mean particle size of ~100 nm and appeared as nanoparticles under transmission electron microscopy, and were positive for CD9, flotillin on western blotting. These exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs), and stimulated HUVECs proliferation and migration. Remarkably, exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10μg/mL) was comparable with that of 5% FBS. According to the known pro-angiogenic miRNAs screening, we found miR378a-3P, miR21-5P, miR132a-3P, miR19b-3P and miR146a-5P were enriched in exosomes compared to hADSCs. Those miRNAs could be intactly transfered into HUVECs via exosomes, and down-regulated the corresponding protein expression in HUVECs. Thereinto, the expression of SUFU which is a target gene of miR378a-3P decreased more than two-thirds, displaying the most significant down-regulation.Meanwhile, the result of miRNAs mimic and inhibitor experiments demonstrated miR378a-3P is the key miRNA in angiogenic activity of exosomes. Taken together, our findings indicate that hADSCs-released exosomes transport pro-angiogenic miRNAs to modulate angiogenesis in recipient cells. These observations may contribute to exploit exosomes as a therapeutic tool for regenerative medicine.
Author Disclosures: F. Xu: None. Q. Xiang: None. X. Long: None. Z. Zhou: None.
- © 2016 by American Heart Association, Inc.