Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine

Abstract

Extracellular vesicles (EVs)-comprising a heterogeneous population of cell-derived lipid vesicles including exosomes, microvesicles, and others-have recently emerged as both mediators of intercellular information transfer in numerous biological systems and vehicles for drug delivery. In both roles, EVs have immense potential to impact tissue engineering and regenerative medicine applications. For example, the therapeutic effects of several progenitor and stem cell-based therapies have been attributed primarily to EVs secreted by these cells, and EVs have been recently reported to play direct roles in injury-induced tissue regeneration processes in multiple physiological systems. In addition, EVs have been utilized for targeted drug delivery in regenerative applications and possess unique potential to be harnessed as patient-derived drug delivery vehicles for personalized medicine. This review discusses EVs in the context of tissue repair and regeneration, including their utilization as drug carriers and their crucial role in cell-based therapies. Furthermore, the article highlights the growing need for bioengineers to understand, consider, and ultimately design and specifically control the activity of EVs to maximize the efficacy of tissue engineering and regenerative therapies.

FIG. 1.

Consideration of extracellular vesicles (EVs) in the design stage of tissue engineering approaches. Tissue engineers consider many parameters in designing therapeutic approaches, including cell source and culture conditions, biomaterial–cell interactions, and the site and method of therapeutic intervention (e.g., injection vs. implantation, use of an alternative anatomical location as an in vivo bioreactor). Consideration of each of these parameters could be affected by further knowledge of how EV biogenesis and cargo may change based on the choices made at each step of the tissue engineering design process. Color images available online at www.liebertpub.com/teb

FIG. 2.

Engineering of EVs for use as therapeutic delivery vehicles in personalized medicine. EVs offer unique potential to be employed as delivery vehicles in personalized medicine. EVs could be obtained from cells harvested from biopsy tissue, loaded with a therapeutic molecule, and injected back into the patient. Such an approach would enable protection of labile therapeutic biologics while also avoiding the immunogenicity inherently associated with synthetic delivery systems. Color images available online at www.liebertpub.com/teb