Novel mesenchymal stem cell based therapies for articular cartilage repair
Once damaged articular cartilage has a limited reparative capacity and thus lesions often progress to arthritis. This has motivated the development of cell based therapies for the repair of cartilage defects such as autologous cho...
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Descripción del proyecto
Once damaged articular cartilage has a limited reparative capacity and thus lesions often progress to arthritis. This has motivated the development of cell based therapies for the repair of cartilage defects such as autologous chondrocyte implantation (ACI). Such therapies are limited in two ways. Firstly, they do not result in the regeneration of hyaline cartilage and hence the repair is temporary. Secondly, widespread adaptation into the clinical setting is impeded by practical issues such as the high fiscal cost and time required for culture expansion of chondrocytes. The applicant is of the belief that both issues cannot currently be addressed by a single new therapy. Therefore the proposed project will put forward separate solutions to both issues. The first theme of the project will determine whether freshly isolated (not culture expanded) infrapatellar fat pad derived cells, embedded in a hydrogel containing microbead-encapsulated growth factors, can used to engineer functional cartilage tissue. A component of this theme will involve magnetic microbead enrichment for cells with surface markers associated with highly chondrogenic cells. Theme 2 of the proposed project will explore an alternative therapy for cartilage defect repair. Specifically, the objective is to tissue engineer in vitro a functional tissue with a zonal structure mimicking that of normal articular cartilage using mesenchymal stem cells. It is hypothesised that such a zonal structure can be generated by controlling the oxygen tension and mechanical environment within the developing tissue. The final theme of the project will be to determine if repairing high-load bearing cartilage defects using either tissue engineering therapies will result in significantly improved repair compared to ACI in a cartilage defect model.