Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions

Extracellular vesicles (EVs) are cell-derived membrane structures exerting major effects in physiological as well as pathological processes by functioning as vehicles for the delivery of biomolecules to their target cells. An increasing number of effects previously attributed to cell-based therapies have been recognized to be actually mediated by EVs derived from the respective cells, suggesting the administration of purified EVs instead of living cells for cell-based therapies. In this review, we focus on the heterogeneity of EVs derived from mesenchymal stem/stromal cells (MSC) and summarize upstream process parameters that crucially affect the resulting therapeutic properties and biological functions. Hereby, we discuss the effects of the cell source, medium composition, 3D culture, bioreactor culture and hypoxia. Furthermore, aspects of the isolation and storage strategies influences EVs are described. Conclusively, optimization of upstream process parameters should focus on controlling MSC-derived EV heterogeneity for specific therapeutic applications.

Automated summary

Extracellular vesicles (EVs) are cell-derived membrane structures that play a major role in physiological and pathological processes by delivering biomolecules to target cells. Many effects previously attributed to cell-based therapies are actually mediated by EVs, suggesting the use of purified EVs instead of living cells for therapy. This review focuses on the heterogeneity of EVs derived from mesenchymal stem/stromal cells (MSC) and summarizes the upstream parameters that critically affect their therapeutic properties and biological functions.