Collagen biomaterial stimulates the production of extracellular vesicles containing microRNA-21 and enhances the proangiogenic function of CD34+ cells

Abstract

CD34+ cells are promising for revascularization therapy, but their clinical use is limited by low cell counts, poor engraftment, and reduced function after transplantation. In this study, a collagen type I biomaterial was used to expand and enhance the function of human peripheral blood CD34+ cells, and potential underlying mechanisms were examined. Compared to the fibronectin control substrate, biomaterial-cultured CD34+ cells from healthy donors had enhanced proliferation, migration toward VEGF, angiogenic potential, and increased secretion of CD63+CD81+ extracellular vesicles (EVs). In the biomaterial-derived EVs, greater levels of the angiogenic microRNAs (miRs), miR-21 and -210, were detected. Notably, biomaterial-cultured CD34+ cells had reduced mRNA and protein levels of Sprouty (Spry)1, which is an miR-21 target and negative regulator of endothelial cell proliferation and angiogenesis. Similar to the results of healthy donor cells, biomaterial culture increased miR-21 and -210 expression in CD34+ cells from patients who underwent coronary artery bypass surgery, which also exhibited improved VEGF-mediated migration and angiogenic capacity. Therefore, collagen biomaterial culture may be useful for expanding the number and enhancing the function of CD34+ cells in patients, possibly mediated through suppression of Spryl activity by EV-derived miR-21. These results may provide a strategy to enhance the therapeutic potency of CD34+ cells for vascular regeneration.—McNeill, B., Ostojic, A., Rayner, K. J., Ruel, M., Suuronen, E. J. Collagen biomaterial stimulates the production of extracellular vesicles containing microRNA-21 and enhances the proangiogenic function of CD34+ cells. FASEB J. 33, 4166–4177 (2019). www.fasebj.org.