UCSF

Stem cell-based therapies are a growing area of interest within regenerative musculoskeletal medicine. Exosomes represent an attractive emergent clinical strategy for the delivery of stem cell-derived growth factors and small molecules to a regenerating tissue environment. Stem cells themselves may not engraft into host tissue but more likely promote a pro-regenerative state through the release of autocrine and paracrine factors. Exosomes, a type of small membrane-bound extracellular vesicle secreted by cells, are of interest as an emergent clinical strategy because they have several key factors that could provide the elusive goal of stem cell therapies in a more practical manner. Exosomes from stem cells appear to have much of the machinery that could promote regenerative capabilities, including growth factors, micro-RNAs (miRNAs), and other signaling molecules that can induce the necessary growth signaling and transcriptional changes to induce a phenotypic change in the local delivery environment. It is important to note that they also have a limited host immune response and can be stored in a freezer, as opposed to many stem cell products that need specialized storage systems to maintain viability. For these reasons, exosome-based therapeutic solutions for rotator cuff repair offer a potential treatment strategy. Recent research provides a highly translational application of exosomes to a chronic rotator cuff repair model and shows efficacy in improving the biomechanical strength of tendon healing at the tendon-bone interface, in addition to partially ameliorating the development of fatty infiltration. Further work is needed to characterize the components of exosomes that result in their bioactivity in addition to considering their cost-effectiveness as a regenerative musculoskeletal treatment.