The secretome of equine bone marrow-derived mesenchymal stem cells enhanced regenerative phenotype of equine articular chondrocytes

Abstract

International audienceEquine osteoarthritis (OA) is a sequential disease which leads to cartilage degradation and painful bone frictions. It induces impaired animal well-being, premature cessation of sport activity, and financial losses. Fibrocartilage synthesis occurring during cartilage destruction is a physiological response, allowing bone protection but reducing tissue mechanical resistance. To date, there is a lack of curative therapies. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to cell itself which can be overcome using their secretomethrough acellular therapy approaches.To understand the effects of equine bone marrow (BM-)MSC secretome on equine articular chondrocytes (eAC) phenotype, indirect co-culture experiments were first performed. Then, we wantedto recapitulate the effects we observed in co-culture on eAC using the MSC-conditioned medium (CM) to make acellular therapy conceivable. We assessed hyaline cartilage and fibrocartilage markers at the transcription and protein levels, and evaluated eAC migratory capacities, which are of interest during OA therapy to favor the filling of the cartilage defects. To optimize immunomodulation properties of MSC secretome for future experiments, MSC priming relevance with interleukin (IL)1-β was evaluated. Suspected to be the principal vectors of the effects observed, exosomes were isolated through chemical precipitation and then characterized to confirm their nature