110 What Is the Evidence From in Vivo Studies That Mesenchymal Stem Cell Derived Extracellular Vesicles Can Facilitate Tendon and Ligament Repair?

Abstract

Abstract Aim Tendon and ligament injury pose an increasingly large burden to society. With surgical repair and grafting susceptible to failure, tissue engineering provides novel avenues for treatment. This systematic review explores evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in animal models. Method A systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase. Risk of bias was assessed using Systematic Review Centre for Laboratory animal Experimentation (SYRCLE). Studies administering EVs isolated from human or animal derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, in silico studies were excluded. Data on isolation and characterisation of MSCs and EVs, and in vivo findings in animal models were extracted. Results Eleven case-control studies were included for analysis. Six studies utilised bone marrow derived MSCs. All studies characterised MSCs via flow cytometry, which expressed CD44 and CD90, and isolated EVs via ultracentrifugation (average diameter 125nm). Five studies utilised histological scoring systems, all of which reported a lower score with EV treatment, suggesting improved healing ability. Four studies reported increased anti-inflammatory cytokine expression (IL-10, TGF-β1); three studies reported decreased endogenous M1/M2 macrophage ratio with EV treatment. Eight studies reported increased maximum stiffness, breaking load, tensile strength in EV-treated tendons. Conclusions MSC-EVs are effective therapeutic agents for tendon/ligament pathologies, attenuating the initial inflammatory response, accelerating tendon matrix regeneration, however evidence linking biomechanical alterations to functional improvement was weak. Future randomised controlled trials are needed to definitely demonstrate MSC-EVs superiority in tendon/ligament injury management.