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Isolation, expansion and characterisation of mesenchymal stem cells from osteoarthritic and osteoporotic donors

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dc.contributor.advisor Coffey, Calvin J.
dc.contributor.advisor Hoey, David A. Coyle, Siobhán 2016-09-14T13:09:14Z 2016-09-14T13:09:14Z 2016
dc.description peer-reviewed en_US
dc.description.abstract Osteoporosis and osteoarthritis are common diseases with significant rates of morbidity associated with same. The search continues for effective treatment strategies for both diseases. Mesenchymal stem cells (MSCs) are critical components in the effective formation and repair of healthy bone and cartilage. Understanding the characteristics and behaviour of MSC’s in osteoarthritic and osteoporotic patients can help delineate and characterise the pathogenesis of these diseases further. The first aim of this study involves the creation of a biobank of osteoporotic and osteoarthritic MSC’s. The second aim includes analysing differentiation potential and cell migration/homing capabilities of these diseased MSC’s. Continuing from these results, a third aim is to explore aspects of how diseased MSC’s may interfere with TGF-β1 signalling, given the potent role of this pathway in regulating bone and cartilage metabolism. Bone marrow aspirates were obtained from osteoarthritic, osteoporotic and healthy donors undergoing scheduled hip surgery in the University of Limerick hospital group. Bone marrow aspirates were extracted through the exposed acetabulum during arthroplasty surgery. MSCs were isolated through standard in vitro culture conditions and underwent characterisation and differentiation as per the criteria outlined by the International Society of Cellular Therapy guidelines. Osteoporotic and osteoarthritic MSCs were then analysed for their osteogenic and adipogenic differentiation potential, migratory capacity and interplay with aspects of TGF-β1 signalling. A total of 10 donors were included in the study with no difficulties or complications arising from obtaining bone marrow aspirates during necessary arthroplasty surgery. MSCs were characterised using flow cytometry and by demonstration of their capacity to differentiate along adipogenic, chondrogenic and osteogenic lineages. Osteoporotic MSCs had an increased propensity to differentiate along the adipogenic lineage in comparison to their osteoarthritic counterparts. Both osteoporotic and osteoarthritic MSCs had altered chemokinetic profiles in comparison to healthy controls. Of particular interest, whilst healthy MSCs migrate towards TGF-β1, osteoporotic MSCs failed to migrate towards this important chemoattractant. The results of this research detail the successful extraction and isolation of MSCs from patients with osteoarthritis and osteoporosis. The surgical location and technique incorporates a transferable skill that could result in largescale collection of both healthy and diseased MSCs. A critical finding includes the altered migration of MSCs towards TGF-β1. This has implications both in the basic understanding of the pathogenesis of osteoporosis and in the development of future therapeutic targets. en_US
dc.language.iso eng en_US
dc.publisher University of Limerick en_US
dc.subject osteoporosis en_US
dc.subject osteoarthritis en_US
dc.subject diseases en_US
dc.subject bone marrow en_US
dc.title Isolation, expansion and characterisation of mesenchymal stem cells from osteoarthritic and osteoporotic donors en_US
dc.type info:eu-repo/semantics/masterThesis en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.type.supercollection ul_theses_dissertations en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US

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