WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?

Victor Lu; Maria Tennyson; James Zhang; Wasim Khan

doi:10.1302/1358-992X.2021.16.045

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WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?

The British Orthopaedic Research Society (BORS) Annual Meeting 2021, held online, 13–14 September 2021.

Victor Lu
Maria Tennyson
James Zhang
Wasim Khan

WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?

Lu V, Tennyson M, Zhang J, Khan W. WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?. Orthop Procs. 2021;103-B(SUPP_16):45-45. doi:10.1302/1358-992X.2021.16.045

Lu, Victor, et al. “WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?.” Orthopaedic Proceedings, vol. 103-B, no. SUPP_16, 2021, pp. 45-45., https://doi.org/10.1302/1358-992X.2021.16.045

Lu, V., Tennyson, M., Zhang, J., & Khan, W. (2021). WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?. Orthopaedic Proceedings, 103-B(SUPP_16), 45-45. https://doi.org/10.1302/1358-992X.2021.16.045

Lu, V., Tennyson, M., Zhang, J. and Khan, W. (2021) “WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?.” Orthopaedic Proceedings, 103-B(SUPP_16), pp. 45-45. Available at: https://doi.org/10.1302/1358-992X.2021.16.045

Lu, Victor, Maria Tennyson, James Zhang, and Wasim Khan. “WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?.” Orthopaedic Proceedings 103-B, no. SUPP_16 (2021): 45-45. https://doi.org/10.1302/1358-992X.2021.16.045

Lu V, Tennyson M, Zhang J, Khan W. WHAT IS THE EVIDENCE FROM IN VIVO STUDIES THAT MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES CAN FACILITATE TENDON AND LIGAMENT REPAIR?. Orthop Procs. 2021 Dec 1;103-B(SUPP_16):45-45. https://doi.org/10.1302/1358-992X.2021.16.045

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Abstract

Objectives

Tendon and ligament injury poses an increasingly large burden to society. With surgical repair and grafting susceptible to high failure rates, tissue engineering provides novel avenues for treatment. This systematic review explores in vivo evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in animal models.

Methods

On May 26th 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, using search terms ‘mesenchymal stem cell’ or ‘multipotent stem cell’ AND ‘extracellular vesicles’ or ‘exosomes’ AND ‘tendon’ or ‘ligament’ or ‘connective tissue’. Risk of bias was assessed using SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. 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, and studies without a control group were excluded. Data on isolation and characterisation of MSCs and EVs, and in vivo findings in animal models were extracted.

Results

Out of 383 relevant studies, 11 case-control studies were included for data extraction, including a total of 448 animal subjects (range 10–90). Six studies utilised bone marrow-derived MSCs. All studies characterised their 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.

Conclusion

MSC-EVs are effective therapeutic agents for tendon/ligament pathologies, attenuating the initial inflammatory response, and accelerating tendon matrix regeneration. Future randomised controlled trials are needed to definitely demonstrate MSC-EVs superiority in management of tendon/ligament injury.