Stem Cell-Derived Extracellular Vesicles as a Novel Potential Therapeutic Tool for Tissue Repair

Abstract

Stem cells, with their therapeutic potential in tissue repair and regeneration, have been widely used in translational medicine. Recent evidence suggests that the beneficial effects are mediated largely by their paracrine actions rather than the engraftment and differentiation at the injured sites. Extracellular vesicles (EVs), actively released from cells, play important roles in cell-to-cell communication and display multiple functions in tissue regeneration. In the present report, we will briefly review the current knowledge related to the therapeutic potential of EVs, particularly stem cell or progenitor cell-derived ones for promoting tissue repair and regeneration, and focus on the restorative properties of exosomes/microvesicles in cutaneous wound healing, bone regeneration, hindlimb ischemia, and vascular injury repair. Stem Cells Translational Medicine 2017;6:1753-1758.

Figure 1

Schematic representation of the main two types of extracellular vesicles released by cells, either by fusion of MVB with the plasma membrane or by direct budding from the plasma membrane. A wide range of cargo is transported within exosomes, including mRNA, miRNA, proteins, etc. Abbreviations: IncRNA, long non‐coding RNA; MHC, major histocompatibility complex; miRNA, microRNA; MVB, multivesicular bodies.

Figure 2

Schematic representation of signaling pathways that were involved in exosomes/MVs mediated pro‐regenerative capacity in cutaneous wound healing, bone regeneration, hindlimb ischemia, and vascular injury repair. The mechanisms of tissue recovery following EVs treatment have been attributed in part to the ability of exosomes/MVs to promote angiogenesis at the site of injury. Exosomes/MVs can promote bone regeneration through modulating the osteogenic differentiation of recipient BMSCs. Exosomes/EVs treatment can promote the cutaneous wound healing process, while excessive scar formation can be prevented in later stages. Exosomes/MVs‐shuttled miRNAs have been demonstrated to reduce inflammation by modulating target proteins in inflammatory signaling pathway during wound healing. Abbreviations: ‐, the specific signaling pathway has not been identified; BMSC, bone marrow mesenchymal stem cell; EV, extracellular vesicle; miRNA, microRNA; MV, microvesicle.