Final Report Summary - STEMREPAIR (Novel mesenchymal stem cell based therapies for articular cartilage repair) The articular cartilage that lines the end of bones in our joints has a limited capacity for repair. This has led to increased interest in the use of cell-based therapies for cartilage regeneration. This project sought to address two of the central challenges impeding the widespread clinical adoption of cell based therapies for articular cartilage regeneration. Firstly, the high fiscal cost and time associated with the isolation and in vitro expansion of cells, and secondly the failure of current approaches to regenerate normal hyaline cartilage. Themes 1 and 2 of the project involved the development of novel approaches to tackle these challenges, while theme 3 of the project involved accessing these new tissue engineering approaches for cartilage regeneration in relevant pre-clinical models. The achievements and outcomes of these three themes are summarised below.Theme 1:As part of this theme, we have demonstrated that it is possible to generate cartilage tissue by combining freshly isolated stromal cells from the infrapatellar fat pad (IFP) of the knee with a porous scaffold, without the need to first expand the cells outside the body. It is envisioned that this combination of a scaffold and freshly isolated IFP cells could be used as an ‘off-the-shelf’ construct for cartilage repair clinically. Theme 2:The objective of theme 2 was to determine if a tissue with a composition and zonal structure mimicking that of normal hyaline cartilage could be engineered using mesenchymal stem cells (MSCs). We found that by modulating both the oxygen levels and the mechanical environment through the depth of stem cell seeded hydrogels in a novel bioreactor, that it was possible to engineer tissues with zonal gradients mimicking certain aspects of normal articular cartilage. We further demonstrated that it was possible to engineer tissues with a zonal structure and depth dependant mechanical properties akin to normal articular cartilage by repopulating decellularized porcine articular cartilage grafts with human stem cells.Theme 3:As part of theme 3, pre-clinical studies to evaluate the efficacy of the novel therapies proposed in theme 1 and 2 of the project were undertaken. We also developed a computational model to predict how environmental cues will regulate chondrogenesis of stem cells in vivo within a load bearing defect.Key project outputs:• 26 peer reviewed publications in leading journals such as Tissue Engineering Part A, Acta Biomaterialia, Advanced Healthcare Materials and European Cells and Materials.• 2 patents filed.
