The microRNA-dependent cell fate of multipotent stromal cells differentiating to endothelial cells

• miRNA expression is different in MSCs, HBs, EPCs, and ECs.
• miRNAs can regulate MSC maintenance and differentiation signal pathways.
• miR-15, -144, -145, and -329 inhibit VEGF-induced differentiation of MSCs into ECs.
• MSCs differentiated by miR-26a and -29b have EC markers and characteristics.

In the endothelial recovery process, bone marrow-derived MSCs are a potential source of cells for both research and therapy, and their capacities to self-renew and to differentiate into all the cell types in the human body make them a promising therapeutic agent for remodeling cellular differentiation and a valuable resource for the treatment of many diseases. Based on the results provided in a miRNA database, we selected miRNAs with unique targets in cell fate-related signaling pathways. The tested miRNAs targeting GSK-3β (miR-26a), platelet-derived growth factor receptor, and CD133 (miR-26a and miR-29b) induced MSC differentiation into functional ECs, whereas miRNAs targeting VEGF receptor (miR-15, miR-144, miR-145, and miR-329) inhibited MSC differentiation into ECs through VEGF stimulation. In addition, the expression levels of these miRNAs were correlated with in vivo physiological endothelial recovery processes. These findings indicate that the miRNA expression profile is distinct for cells in different stages of differentiation from MSCs to ECs and that specific miRNAs can function as regulators of endothelialization.

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