Mesenchymal stem cell-derived small extracellular vesicles and bone regeneration

Mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs) are promising candidates for cell-based and cell-free regenerative medicine, respectively. By virtue of their multiple lineage differentiation capacity, MSCs have been implicated as an ideal tool for bone and cartilage regeneration. However, later observations attributed such regenerative effects to MSC-secreted paracrine factors. Exosomes, endosomal originated sEVs carrying lipid, protein and nucleic acid cargoes, were identified as components of the MSC secretome and propagated the key regenerative and immunoregulatory characteristics of parental MSCs. Here, exosome biogenesis, the molecular composition of exosomes, sEV-cell interactions and the effects on key bone homeostasis cells are reviewed. MSC-derived sEVs show to promote neovascularization and bone and cartilage regeneration in preclinical disease models. The mechanisms include the transfer of molecules, including microRNAs, mRNAs and proteins, to other key cells. MSC-derived sEVs are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials. Although major exploratory efforts have been made for therapeutic development, the secretion, distribution and biological effects of MSC-derived sEVs in bone and cartilage regeneration are not fully understood. Moreover, techniques for high-yield production, purity and storage need to be optimized before effective and safe MSC-derived sEVs therapies are realized.