Abstract
Extracellular vesicles (EV) consist of exosomes, which are released upon fusion of the multivesicular body with the cell membrane, and microvesicles, which are released directly from the cell membrane. EV can mediate cell–cell communication and are involved in many processes, including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. The vast amount of processes that EV are involved in and the versatility of manner in which they can influence the behavior of recipient cells make EV an interesting source for both therapeutic and diagnostic applications. Successes in the fields of tumor biology and immunology sparked the exploration of the potential of EV in the field of regenerative medicine. Indeed, EV are involved in restoring tissue and organ damage, and may partially explain the paracrine effects observed in stem cell-based therapeutic approaches. The function and content of EV may also harbor information that can be used in tissue engineering, in which paracrine signaling is employed to modulate cell recruitment, differentiation, and proliferation. In this review, we discuss the function and role of EV in regenerative medicine and elaborate on potential applications in tissue engineering.
Highlights
Regenerative medicine aims at the functional restoration of a damaged, malfunctioning, or missing tissue
As transplantation techniques for other organs developed over the following decades, the limiting factor for these procedures shifted from technical limitations to the supply of suitable organs and tissues
We recently demonstrated that endothelial cell-derived exosomes induced angiogenesis by inhibition of cellular senescence, and that transfer of miR-214 downregulated ataxia telangiectasia mutated (ATM) expression in recipient cells, resulting in decreased cellular senescence [13]
Summary
Regenerative medicine aims at the functional restoration of a damaged, malfunctioning, or missing tissue. Bone marrow MSC-derived exosomes were able to decrease apoptosis and increase cell proliferation in an acute kidney injury model, and the authors hypothesized that this was the result of exosome-mediated RNA transfer [83]. Exosomes derived from tubular epithelial cells stimulated with hypoxia activated fibroblasts through TGF-β1 signaling, resulting in increased fibroblast proliferation, which could aid in acceleration of tissue repair [91] These studies indicate that EV play a role in local tissue repair through regulation of cell proliferation. Besides molecules responsible for ECM interaction, EV have been shown to express ECM-remodeling proteins, like matrix metalloproteinases (MMPs), which can degrade collagens, elastin, fibronectin, and laminin These processes are important in ECM re-structuring, as well as cytokine release, angiogenesis, and cell migration [112, 113]. EXTRACELLULAR VESICLES POTENTIAL All in all, EV show great potential for a role in regenerative medicine because of their role in cell recruitment, differentiation, and www.frontiersin.org
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