Effect of extracellular matrices on production and potency of mesenchymal stem cell-derived exosomes

Mesenchymal stem cell (MSC) derived exosomes have emerged as potential acellular therapeutics for various tissue regenerative applications. However, successful clinical translation of exosome-based therapy is limited by lack of a structured production platform. Thus, in this study, the effect of decellularized extracellular matrix (dECM) was assessed on the production and potency of exosomes secreted by bone marrow-derived human MSCs. The results indicate that there was a ∼2-fold increase in MSC-exosome production when MSCs were cultured on dECM compared to TCP. Further, our study revealed that dECM generation induced by ascorbic acid (AA) up to 100 µg mL^-1 highly increased exosome yield thereby indicating a potential scale up method for MSC exosome production. The bioactivity of exosomes was investigated by their ability to improve the healing of wounded human skin explants. Wound closure was enhanced in the presence of exosomes isolated from MSCs cultured on ascorbic acid-induced dECM compared to TCP generated MSC-exosomes. In summary, this study suggests a promising solution to a major bottleneck in large-scale production of MSC exosomes for cell-free therapy.