Clarke, Emily-Jayne
(2023)
Exploring the Role of Extracellular Vesicles in Equine Musculoskeletal Pathologies and Associated Regenerative Therapies.
Doctor of Philosophy thesis, University of Liverpool.
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Abstract
Horses are used in a variety of disciplines, including dressage, show jumping, eventing and racing. Thus, the equine athlete is predisposed to the development of musculoskeletal injury. Both equine osteoarthritis and tendon injury are significant causes of pain, lameness and are equine welfare concerns. Osteoarthritis and tendon injuries are usually diagnosed at late stage and treatment includes biological therapies, such as mesenchymal stem cell and platelet-rich plasma therapy. These therapeutics often produce variable clinical outcomes and their mechanistic action is not well characterised. It is hypothesised that extracellular vesicles may be involved in mediating the effect of biological therapies, and could offer a viable cell-free alternative therapeutic. The aims of this thesis were as follows; (1) To investigate extracellular vesicle structure and protein cargo from a longitudinal in vivo model of equine osteoarthritis treated with mesenchymal stem cells, in order to determine disease-associated extracellular vesicle cargo, and their potential role in mediating mesenchymal stem cell therapy. (2) Explore the differences in composition of extracellular vesicles from healthy horses and those with clinically diagnosed osteoarthritis using both spectroscopic and spectrometric techniques. (3) Explore the composition of platelet-rich plasma and platelet-rich plasma derived extracellular vesicles using mass spectrometry proteomics. (4) Investigate the effect of platelet-rich plasma and platelet-rich plasma derived extracellular vesicles in an in vitro model of equine tendon injury, using mass spectrometry proteomics and gene expression analysis. Extracellular vesicles were characterised and a range of spectroscopic and spectrometric techniques used including mass spectrometry. This thesis has catalogued extracellular vesicle cargo from synovial fluid in both an in vivo models of equine osteoarthritis (carpal osteochondral fragment model) and naturally occurring disease. As some protein content can be attributed to disease progression they could serve as potential biomarkers used in the development of diagnostic tests to aid earlier diagnosis and intervention in osteoarthritis. Further to this, my work has identified altered cargo in association with extracellular vesicles following mesenchymal stem cell treatment, and cellular cargo following platelet-rich plasma derived extracellular vesicle treatment, emphasising their role as mediators of therapy and their capacity to serve as future therapeutics. Therefore, they might be considered as a viable therapeutic alternative that warrants further investigation in the case of mesenchymal stem cell therapy, in order to deliver a safer more reproducible therapeutic. With respect to platelet-rich plasma, extracellular vesicles should be considered when optimising the composition of platelet-rich plasma for more efficacious outcomes, or considered as an alternative to platelet rich plasma.
| Item Type: | Thesis (Doctor of Philosophy) |
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| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Jan 2024 11:56 |
| Last Modified: | 10 Jan 2024 11:56 |
| DOI: | 10.17638/03177549 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3177549 |
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