Inflammatory priming enhances mesenchymal stromal cell secretome potential as a clinical product for regenerative medicine approaches through secreted factors and EV-miRNAs: the example of joint disease

The study investigated the potential of mesenchymal stromal cell (MSC) secretome, particularly from adipose-derived MSCs (ASCs), for regenerative medicine in joint diseases like osteoarthritis. It involved isolating ASCs from four donors and analyzing their secreted factors and extracellular vesicle (EV)-embedded miRNAs, both before and after priming with IFNγ. Results showed that IFNγ priming enhanced the secretome's anti-inflammatory and regenerative properties, promoting cell motility and modulating inflammatory processes. The secretome contained over 60 cytokines/chemokines and more than 240 miRNAs, with key factors like FST, TIMP2, and IGFBP4 being highlighted. In vitro experiments demonstrated that the primed secretome could shift macrophage polarization from a pro-inflammatory to an anti-inflammatory phenotype, suggesting enhanced therapeutic potential. Overall, the findings indicated that IFNγ-primed MSC secretomes could offer protective effects in osteoarthritis by modulating immune responses and supporting cartilage health, making it a promising cell-free therapeutic option for conditions involving inflammation and tissue degeneration.