Importance of stem cell culture conditions for their derived extracellular vesicles therapeutic effect

Stem cell-derived extracellular vesicles (EVs) could be enhanced by modifying specific in vitro parameters when culturing their originating stem cells. Controlling stem cell growth conditions with physical properties, oxygen tension and media preconditioning with soluble factors may influence EVs biogenesis and EVs biological function as well. Unfortunately, many misconceptions and methodological issues have hampered the progress in understanding the biological properties of EVs. In this review we will first discuss the major concerns involved in a suitable EVs production from stem cell culture. Then, we will describe the current techniques for EV isolation, focusing on their advantages and disadvantages, as well as their impact on EVs yield, recovery and functionality. Standardization of the methodology is a prerequisite to compare, to validate and to improve the reliability and credibility of all the different findings reported for the development of EV-based therapeutics.