Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles.

BACKGROUND: Extracellular vesicles (EVs) are promising therapeutics for diseases associated with inflammation and tissue remodeling. However, a major limitation for the clinical translation of EV therapeutics is heterogeneity, which is donor dependent. In this study we sought to assess the physiochemical characteristics and therapeutic efficacy of tissue-derived EVs from different donors. Donor-dependent therapeutic effects of cell culture and biofluid-derived EVs have previously been shown, but remains largely unknown for tissue-derived EVs. We obtained EV-enriched samples from various sources of adipose tissue and examined their effect in reducing inflammation in a highly translational model of myocarditis. RESULTS: We demonstrate that the molecular composition of EVs varies depending on the donor and that therapeutic efficiency is donor-dependent even when controlling for age and sex. CONCLUSIONS: Our findings indicate that further research is needed to identify critical donor characteristics that predict therapeutic ability of individual or pooled adipose tissue-derived EVs to reduce inflammation and fibrosis.