Human Umbilical Cord Mesenchymal Stem Cells-Derived Small Extracellular Vesicles Can Be Considered as Cell-Free Therapeutics for Angiogenesis Promotion

Objective: Angiogenesis has critical roles in several physiological processes. Restoring angiogenesis in somepathological conditions such as a few vascular diseases can be a therapeutic approach to controlling this issue.Mesenchymal stem cells (MSCs) secrete specific intracellular products known as extracellular vesicles (EVs) with hightherapeutic potential which compared to their source cells, do not have the limitations of cell therapy. The angiogeniceffect of the human umbilical cord MSCs (hUCMSCs)-derived small EVs are evaluated in the present work. Aim of thisresearch is to show that hUCMSCs-derived small EVs cause differentiation of genes involved in angiogenesis likeFGFR-1, FGF, VEGF, and VEGFR-2.Materials and Methods:In this experimental study, MSCs were isolated from the human umbilical cord, and afterconfirming their identities, their secreted EVs (including exosomes) were extracted by ultracentrifugation. The isolatedsmall EVs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), bicinchoninicacid assay (BCA), and Western Blotting. Then, the human umbilical vein endothelial cells (HUVECs) were treatedwith derived small EVs for 72 hours, and the expression of the angiogenic factors including FGFR-1, FGF, VEGF,and VEGFR-2 was evaluated by quantitative real-time-polymerase chain reaction (qPCR). Angiogenesis was alsoevaluated via a tube formation assay.Results: The results demonstrated that FGFR-1, FGF, VEGF, and VEGFR-2 could be elevated 2, 2, 3.5, and 2 times,respectively, in EVs treated HUVECs, and derivative EVs can encourage tube formation in HUVECs.Conclusion: These findings imply that hUCMSCs-derived small EVs are valuable resources in promoting angiogenesisand are very promising in cell-free therapy.

Abstract licence: CC BY-NC

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