Osteoarthritis (OA) is a debilitating joint disease characterised by pain and progressive destruction of elements such as articular cartilage. Autologous chondrocyte implantation is a cellular therapy developed to regenerate damaged cartilage and delay or negate the need for a total joint replacement. The use of mesenchymal stem cells (MSCs) provides an alternative to harvesting healthy cartilage in order to obtain chondrocytes for transplantation. In this thesis, the chondrogenic and immunomodulatory properties of human bone marrow (BM-MSCs), infrapatellar fat pad (FP-MSCs), subcutaneous fat (SCF-MSCs) and synovial fluid (SF-MSCs) derived mesenchymal stem/stomal cells were characterised to determine their suitability for cartilage repair. Synovial inflammation and the prevalence of macrophage subsets were determined in the synovium and infrapatellar fat pad from patients with and without OA.
FP-MSCs and SF-MSCs from the same donor differed with regards to in vitro proliferation and their response to a proinflammatory stimulus. None of the MSC populations examined displayed levels of chondrogenic potency that were akin to their matched chondrocyte counterparts, although BM-MSCs and FP-MSCs did show a more enhanced ability to undergo chondrogenesis than SCF-MSCs and SF-MSCs. Additionally, the expression of certain surface markers commonly associated with chondrogenic potency in chondrocytes, such as CD44, were not indicative of the chondrogenic propensity of MSCs. Analyses of the phenotype of macrophages in human synovium and FP showed a co-existence of pro- (M1) and anti-inflammatory (M2) cells in both tissues. However, cell surface markers employed in the study did not permit a clear distinction between M1 and M2 cells. Image analyses revealed that the obesity related hypertrophy observed in adipocytes from subcutaneous fat, does not occur in adipocytes in the FP. To conclude, the results presented in this thesis adds
to current knowledge of joint derived stem cells and immune cells
