Comparison of two ASC-derived therapeutics in an in vitro OA model: secretome versus extracellular vesicles

 In the last years, several clinical trials have proved the safety and efficacy of Adipose-derived Stem/Stromal Cells (ASC) in contrasting osteoarthritis (OA). Since ASC act mainly through paracrine mecha-nisms, their secretome (conditioned medium, CM) represents a promising therapeutic alternative. ASC-CM is a complex cocktail of proteins, nucleic acids and lipids released as soluble factors and/or conveyed into extracellular vesicles (EV). Here we investigate its therapeutic potential in an in vitro model of OA. Human articular chondrocytes (CH) were induced towards an OA phenotype by 10ng/ml TNFα in the pres-ence of either ASC-CM or EV, both deriving from 5x105 cells, to evaluate the effect on hypertrophic, cata-bolic and inflammatory markers. Given the same number of donor cells, our data reveal a higher therapeutic potential of ASC-CM compared to EV alone, that was confirmed by its enrichment in chondro-protective factors among which TIMP-1 and -2 stand out. In details, only ASC-CM significantly decreased MMP activity (22% and 29% after 3 and 6 days) and PGE2 expression (up to 40% at day 6) boosted by the inflammatory cytokine. Conversely, both treatments down-modulated of ~30% the hypertrophic marker COL10A1. These biological and molecular evidences of ASC-CM beneficial action on CH with an induced OA phenotype may lay the basis for its future clinical translation as a cell-free therapeutic in the management of OA.