Behind the Scenes of Extracellular Vesicle Therapy for Skin Injuries and Disorders

Abstract

Significance: Skin wounds and disorders compromise the protective functions of skin and patient quality of life. Although accessible on the surface, they are challenging to address due to paucity of effective therapies. Exogenous extracellular vesicles (EVs) and cell-free derivatives of adult multipotent stromal cells (MSCs) are developing as a treatment modality. Knowledge of origin MSCs, EV processing, and mode of action is necessary for directed use of EVs in preclinical studies and methodical translation. Recent Advances: Nanoscale to microscale EVs, although from nonskin cells, induce functional responses in cutaneous wound cellular milieu. EVs allow a shift from cell-based to cell-free/derived modalities by carrying the MSC beneficial factors but eliminating risks associated with MSC transplantation. EVs have demonstrated striking efficacy in resolution of preclinical wound models, specifically within the complexity of skin structure and wound pathology. Critical Issues: To facilitate comparison across studies, tissue sources and processing of MSCs, culture conditions, isolation and preparations of EVs, and vesicle sizes require standardization as these criteria influence EV types and contents, and potentially determine the induced biological responses. Procedural parameters for all steps preceding the actual therapeutic administration may be the key to generating EVs that demonstrate consistent efficacy through known mechanisms. We provide a comprehensive review of such parameters and the subsequent tissue, cellular and molecular impact of the derived EVs in different skin wounds/disorders. Future Directions: We will gain more complete knowledge of EV-induced effects in skin, and specificity for different wounds/conditions. The safety and efficacy of current preclinical xenogenic applications will favor translation into allogenic clinical applications of EVs as a biologic.

Stem cells and extracellular vesicles to improve preclinical orofacial soft tissue healing

“…The final study applied MSC EVs as enhancers of bone formation in bone grafting (NCT04998058). With such few ongoing trials, there is a real opportunity for future clinical trials to translate the promising findings observed in EV therapeutics in soft tissue areas such as the skin [ 123 ], tendon [ 124 ], heart [ 125 ] or liver [ 126 ] to the orofacial soft tissues.…”