Versatility of mesenchymal stem cell-derived extracellular vesicles in tissue repair and regenerative applications

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic cells that have been widely explored in the field of regenerative medicine. MSCs possess the ability to secrete soluble factors as well as lipid bound extracellular vesicles (EVs). MSCs have gained increased interest and attention as a result of their therapeutic properties, which are thought to be attributed to their secretome. However, while the use of MSCs as whole cells pose heterogeneity concerns and survival issues post-transplantation, such limi-tations are absent in cell-free EV-based treatments. EVs derived from MSCs are promising therapeutic agents for a range of clinical conditions and disorders owing to their immunomodulatory, pro -regenerative, anti-inflammatory, and antifibrotic activity. Recent successes with preclinical studies us-ing EVs for repair and regeneration of damaged tissues such as cardiac tissue, lung, liver, pancreas, bone, skin, cornea, and blood diseases are discussed in this review. We also discuss delivery strategies of EVs using biomaterials as delivery vehicles through systemic or local administration. Despite its effectiveness in preclinical investigations, the application of MSC-EV in clinical settings will necessitate careful consideration surrounding issues such as: i) scalability and isolation, ii) biodistribution, iii) targeting specific tissues, iv) quantification and characterization, and v) safety and efficacy of dosage. The future of EVs in regenerative medicine is promising yet still needs further investigation on enhancing the efficacy, scalability, and potency for clinical applications. (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic cells that secrete soluble factors and lipid bound extracellular vesicles (EVs). MSC-EVs have gained interest for their therapeutic properties in regenerative medicine, offering immunomodulatory, pro-regenerative, anti-inflammatory, and antifibrotic effects. This review discusses the successful use of MSC-EVs in preclinical studies for tissue repair and regeneration, as well as delivery strategies using biomaterials. However, further investigation is needed to address scalability, biodistribution, tissue targeting, quantification, characterization, safety, and efficacy of MSC-EVs for clinical applications.