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Title: Tendon and ligament stem cells and their niche
Author: Lee, Katie Joanna
ISNI:       0000 0004 6495 9237
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Tendon and ligament are prone to age- and injury-related degeneration. Tendon and ligament are unable to heal effectively after injury and current treatment strategies have variable success rates. The identification of stem cell populations in tendon and ligament holds potential for new therapeutic strategies to treat tendon and ligament injuries. The stem cell niche has been shown to be vital for survival and function of a number of stem cell populations, including tendon. Modulation of the stem cell niche can induce changes in stem cell phenotype and function and holds therapeutic potential. The aim of this study was to characterise stem cell populations in equine superficial digital flexor tendon (SDFT) and canine cranial cruciate ligament (CCL), as well as characterise the stem cell niche of these cell populations. Tendon- and ligament-derived stem cells (TDSCs and LDSCs respectively) and tenocytes and ligamentocytes (tendon and ligament fibroblasts respectively) were isolated from tendon and ligament tissue and assessed for clonogenicity, proliferation, stem cell and tenogenic marker expression and multipotency. The extracellular matrix niche of the different ligament cell populations was also investigated using metabolic labelling and proteomic analysis. Cell populations isolated from equine SDFT demonstrated many properties of stem cells however differentiation potential was restricted. There were very few differences in stemness and niche composition between TDSCs and tenocytes suggesting a heterogeneous mixture of cells within equine SDFT at different stages of differentiation. LDSCs isolated from canine CCL demonstrated all of the hallmarks of a stem cell and differed in phenotype and gene expression to ligamentocytes which showed reduced stemness. The proteomic composition of the LDSC and ligamentocyte niche was similar with differential expression and turnover of some extracellular matrix proteins between cell types. These results indicate the presence of two cell populations and niches within canine CCL. Stem cell populations present in equine tendon and canine ligament may hold therapeutic potential and modulation of the stem cell niche in these tissues may provide a less invasive alternative treatment strategy than current therapies.
Supervisor: Laird, E. G. ; Comerford, E. J. ; Clegg, P. D. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral