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Evaluation of the potential for repair of degenerate hyaline cartilage in the osteoarthritic knee by cartilage stem cells

Nelson, Larissa 2012. Evaluation of the potential for repair of degenerate hyaline cartilage in the osteoarthritic knee by cartilage stem cells. PhD Thesis, Cardiff University.
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Osteoarthritis (OA) is a highly prevalent, debilitating disease affecting many joints including the knee. Despite the involvement of several tissues, it is believed that the articular cartilage is the primary site of pathogenesis in humans. Within this study, a new scoring system of OA was devised, incorporating the articular cartilage and underlying bone, aimed at providing a more comprehensive means of grading the severity of tissue damage. We examined changes progressively from mild to severe and were able to deduce from the scoring system that bone changes may precede those of the overlying cartilage. Immunohistochemistry was used to assess stem cell marker expression, proliferation and progressive changes within the extracellular matrix of sectioned osteochondral plugs, however no distinct pattern of change could be extrapolated, highlighting the variable nature of this taxing disease. Previous studies have demonstrated the presence of a sub-population of chondroprogenitor cells present in normal hyaline cartilage. We demonstrated in this study that a similar group of cells reside in osteoarthritic articular cartilage. We were able to isolate and expand clonally derived primary cell lines to beyond 50 population doublings whilst maintaining a chondrogenic phenotype, and demonstrated the tri-lineage potential of these cells. That said, a significant amount of variation was observed and it was, therefore, postulated that there may be a smaller cohort of viable cells within this sub-population isolated from osteoarthritic cartilage. A preliminary study was also carried out comparing chondroprogenitors from normal articular cartilage to those isolated from OA tissue. Heterogeneity was again encountered, suggesting that there was a group of OA chondroprogenitors with similar characteristics to the normal cells, which differed from the other less metabolically active cells. This finding was agreeable with the aforementioned postulation. Data from our preliminary integration study was promising as we demonstrated the potential for using these chondroprogenitor cells in combination with other cells whilst achieving successful integration. However, further work is necessary to distinguish between the cell lines with the potential for integration from those that lacked this ability, thereby eliminating the heterogeneity. The presence of viable chondroprogenitor cells in OA tissue challenges the dogma that the tissue is irrecoverable, and opens the scope for regenerative medicine using resident progenitor cells. This is an exciting prospect that could significantly contribute to articular cartilage repair.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
Uncontrolled Keywords: Articular cartilage; Osteoarthritis Chondroprogenitor
Funders: British Orthopaedic Association, Joint Action
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 04:39

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