Preclinical Evidence of MSC-Derived Exosomes

Extracellular vesicles (EVs) are small membrane-enclosed particles released by cells for intercellular communication, and they carry a variety of bioactive molecules. As they often possess the same capacity as their parent cells, mesenchymal stromal/stem cell (MSC)-derived EVs are a popular cell-free alternative for the treatment of various musculoskeletal pathologies due to their regenerative, anti-inflammatory, and immunomodulatory capacities. This chapter provides an overview of the preclinical evidence available on MSC-derived EVs, with a focus on in vivo experimental models for the repair of cartilage and bone defects, and treatment of osteoarthritis, ligament and tendon pathologies, and osteoporosis. Most studies were performed in vitro or in small animal models and found therapeutic effects of MSC-EVs. No dedicated safety-related biodistribution or tumorigenesis studies have been published, but no concerns on biodistribution or adverse reactions have been published either. However, MSC-EVs can stimulate osteosarcoma cells. Many different factors have been suggested to play a role in the molecular mechanisms of MSC-EVs, such as various microRNAs, growth factors, and mitochondrial transfer. In orthopedic and sports medicine applications, the immunomodulatory effects, especially the polarization of macrophages to the anti-inflammatory M2 subtype, seem to be one of the main beneficial effects of MSC-EVs.