Regenerative medicine 2.0: extracellular vesicle–based therapeutics for musculoskeletal tissue regeneration

Abstract

In recent years, extracellular vesicles (EVs) have emerged as prominent mediators of the homeostasis, repair, and regeneration of musculoskeletal tissues including bone, skeletal muscle, and cartilage. Accordingly, the therapeutic potential of EVs for regenerative medicine applications has not gone unnoticed. The use of EVs for the treatment of musculoskeletal injury and disease in veterinary species is a nascent but rapidly expanding area of research. Recent studies in this area have demonstrated the safety and feasibility of EV products in dogs and horses. While early clinical responses to EV-based therapeutics in companion animals have been favorable, more rigorously designed, sufficiently powered, and placebo-controlled clinical trials are required to fully elucidate the clinical benefits and best-use scenarios for EV therapeutics in veterinary medicine. Additionally, clinical translation of EV-based therapeutics will require Good Manufacturing Practice–compliant methods to scale up and purify EV products. Despite these challenges, EVs hold great promise in the regenerative medicine landscape, particularly in the treatment of musculoskeletal injury and disease in companion animals.

Equine mesenchymal stem cell derived extracellular vesicle immunopathology biomarker discovery

“…In the presence of inflammatory cytokines, MSCs demonstrate immunomodulating properties, particularly the ability to inhibit inflammation and promote anti‐inflammatory responses (Han et al., 2019 ; Li & Hua, 2017 ; Qi et al., 2018 ). The ability of MSCs to differentiate into several lineages, coupled with their roles in immunomodulation and reducing inflammation in damaged tissue, sparked their translation into clinical applications (Han et al., 2019 ; Qi et al., 2018 ; Williams & Ehrhart, 2022 ). For example, they have been investigated for their potential in assisting regenerative processes, including repairing damage in musculoskeletal tissue, cardiac systems, the liver, cornea and trachea (Han et al., 2019 ).…”

“…Despite the perceived involvement of MSCs in immunomodulation, their delivery to target destinations remains low when administered. This suggests that the tropic factors secreted by MSCs, collectively labelled the secretome, are likely responsible for these effects (Gowen et al., 2020 ; Kearney et al., 2022 ; Williams & Ehrhart, 2022 ). The secretome contains mediators and extracellular vesicles (EVs), the latter of which include exosomes and microvesicles (Arévalo‐Turrubiarte et al., 2022 ; Kearney et al., 2022 ; Soukup et al., 2022 ).…”

Mechanical strain drives exosome production, function, and miRNA cargo in C2C12 muscle progenitor cells

“…One such area where exosomes hold therapeutic promise is musculoskeletal regeneration 21 . During aging, the tissue quality and regenerative capacity of skeletal muscle and bone are severely compromised 22,23 .…”

“…One such area where exosomes hold therapeutic promise is musculoskeletal regeneration. 21 During aging, the tissue quality and regenerative capacity of skeletal muscle and bone are severely compromised. 22,23 This contributes to age-related muscle loss and dysfunction, termed sarcopenia, as well as osteoporosis, which together are linked to frailty, increased risk of fracture, and increased mortality.…”