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

Document Type : Original Article


1 Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran


Angiogenesis has critical roles in several physiological processes. Restoring angiogenesis in some
pathological 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 high
therapeutic potential which compared to their source cells, do not have the limitations of cell therapy. The angiogenic
effect of the human umbilical cord MSCs (hUCMSCs)-derived small EVs are evaluated in the present work. Aim of this
research is to show that hUCMSCs-derived small EVs cause differentiation of genes involved in angiogenesis like

Materials and Methods:
In this experimental study, MSCs were isolated from the human umbilical cord, and after
confirming their identities, their secreted EVs (including exosomes) were extracted by ultracentrifugation. The isolated
small EVs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), bicinchoninic
acid assay (BCA), and Western Blotting. Then, the human umbilical vein endothelial cells (HUVECs) were treated
with 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 also
evaluated via a tube formation assay.

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.

These findings imply that hUCMSCs-derived small EVs are valuable resources in promoting angiogenesis
and are very promising in cell-free therapy.


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