Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal cells as carriers for Paclitaxel delivery

Abstract

Background: Mesenchymal Stromal Cells (MSC)-derived Extracellular Vesicles (EV) represent innovative tools for drug delivery systems. However, their clinical use is limited by the lack of standardized good manufacturing practice (GMP)-compliant isolation and conservation protocols. In this study, we developed a GMP-compliant protocol for the preparation of MSC-EVs and investigated the feasibility of producing EVs loaded with paclitaxel (PTX) for clinical application as drug products. Methods: Adipose tissues from 13 donors were used to obtain MSC-EVs via culture supernatant ultracentrifugation. EVs loaded with PTX were manufactured by adding the drug to the culture medium of MSCs before supernatant collection. EV identity was verified in terms of concentration/size, protein content, morphology, and expression of EV surface markers. The anti-proliferative activity, accumulation ability in tumor cells and PTX content, as well as their stability over time, were also evaluated. Results: High numbers of EV/EV-PTX compliant in terms of integrity/identity were obtained and can be successfully stored for up to one year at -80 °C. Cellular studies have shown that EVs are capable of accumulating in tumor cells and, when loaded with PTX, inhibiting the proliferation of a pleural mesothelioma cell line. Conclusions: These results support the potential future clinical use of EVs as carriers for drug delivery to improve cancer treatment strategies.