CHAPTER 6: Mesenchymal Stromal Cell (MSC)-derived Small Extracellular Vesicles as Next-generation Therapeutics for Cartilage Regeneration

Mesenchymal stromal/stem cells (MSCs) are currently the most tested cell type in regenerative medicine and have demonstrated therapeutic efficacy for a wide spectrum of injuries/diseases including cartilage injuries and osteoarthritis, with an established safety record in human patients. Although MSCs were originally predicated to mediate tissue repair through cell differentiation and replacement, it is now evident and widely accepted that these cells exert paracrine effects on tissue repair, mainly through the release of 50–200 nm small extracellular vesicles (sEVs). Here, we highlight the application of MSC therapies, focusing on their roles in animal models of cartilage defects and osteoarthritis, as well as recent developments of MSC therapies in clinical studies. Furthermore, we will expand on our understanding of mechanisms of action of MSCs in tissue repair, presenting the latest progress in development of MSC-sEVs as a next-generation cell-free therapy for cartilage regeneration.