Comparative effect of platelet and mesenchymal stromal cells derived extracellular vesicles on human cartilage explants using an ex vivo inflammatory osteoarthritis model.

Aims: Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cells (MSCs)-derived EVs have been studied as an alternative for osteoarthritis treatment. However, its clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for osteoarthritis (OA) by comparing its effects to that of human umbilical cord MSC-derived EVs (cEVs) on ex vivo OA-induced model using human cartilage explants. Methods: pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized. OA conditions were induced to human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml TNFα) and treated with 1x109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG) and collagen cartilage content were quantified, and a histological study was performed. EVs uptake was monitored using PKH-26 labelled EVs. Results: Higher content of DNA and collagen was observed for the pEVs treated group compared to control and cEVs groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion: In conclusion, pEVs show better performance than cEVs in our in vitro OA-model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine.