Due to their immune-evasive nature, MSCs release immunomodulatory factors which allow them to escape rejection mechanisms for sufficient time to exert their therapeutic action ( Ankrum et al., 2014). Since described by Friedenstein ( Friedenstein et al., 1966), mesenchymal stem/stromal cells (MSCs) have been the focus of research efforts to exploit their therapeutic potential. This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. However, the consistent lack of engraftment indicates that the observed effect is delivered through a “hit-and-run” mechanism, by a temporal release of paracrine molecules. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments. 2Centre for Research in Medical Devices (CÚRAM), Biosciences, National University of Ireland Galway, Galway, Ireland.1Regenerative Medicine Institute (REMEDI), Biosciences, National University of Ireland Galway, Galway, Ireland.Patrizio Mancuso 1,2 *, Swarna Raman 1, Aoife Glynn 1, Frank Barry 1,2 and J.
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