Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles

Growing evidence indicates that intracellular signaling mediated by extracellular vesicles (evs) released by stem cells plays a considerable role in triggering the regenerative program upon transplantation. evs from umbilical cord mesenchymal stem cells (uc-msc-evs) have been shown to enhance tissue repair in animal models. however, translating such results into clinical practice requires optimized ev collection procedures devoid of animal-originating agents. thus, in this study, we analyzed the influence of xeno-free expansion media on biological properties of uc-mscs and uc-msc-evs for future applications in cardiac repair in humans. our results show that proliferation, differentiation, phenotype stability, and cytokine secretion by uc-mscs vary depending on the type of xeno-free media. importantly, we found distinct molecular and functional properties of xeno-free uc-msc-evs including enhanced cardiomyogenic and angiogenic potential impacting on target cells, which be explained by elevated concentration of several pro-cardiogenic and pro-angiogenic microrna (mirnas) present in the evs. our data also suggest predominantly low immunogenic capacity of certain xeno-free uc-msc-evs reflected by their inhibitory effect on proliferation of immune cells in vitro. summarizing, conscious selection of cell culture conditions is required to harvest uc-msc-evs with the optimal desired properties including enhanced cardiac and angiogenic capacity, suitable for tissue regeneration.