A call for standardization for secretome and extracellular vesicles in osteoarthritis: results show disease-modifying potential, but protocols are too heterogeneous—a systematic review

The currently available osteoarthritis (OA) treatments offer symptoms’ relief without disease-modifying effects. Increasing evidence supports the role of human mesenchymal stem cells (MSCs) to drive beneficial effects provided by their secretome and extracellular vesicles (EVs), which includes trophic and biologically active factors. Aim of this study was to evaluate the in vitro literature to understand the potential of human secretome and EVs for OA treatment and identify trends, gaps, and potential translational challenges. A systematic review was performed on PubMed, Embase, and Web-of-Science, identifying 58 studies. The effects of secretome and EVs were analysed on osteoarthritic cells regarding anabolic, anti-apoptotic/anti-inflammatory and catabolic/pro-inflammatory/degenerative activity, chondroinduction, and immunomodulation. The results showed that MSC-derived EVs elicit an increase in proliferation and migration, reduction of cell death and inflammation, downregulation of catabolic pathways, regulation of immunomodulation, and promotion of anabolic processes in arthritic cells. However, a high heterogeneity in several technical or more applicative aspects emerged. In conclusion, the use of human secretome and EVs as strategy to address OA processes has overall positive effects and disease-modifying potential. However, it is crucial to reduce protocol variability and strive toward a higher standardization, which will be essential for the translation of this promising OA treatment from the in vitro research setting to the clinical practice. Graphical Abstract: (Figure presented.)