Articular cartilage is a white connective tissue covering the ends of long bones to facilitate movement and articulation. Due to the avascular nature of the tissue, it has a limited capacity to repair once damaged. Human induced pluripotent stem cells are suggested as an ethical and ultimate source for cell based-therapies. Tissue engineering using these cells might present as a promising treatment for cartilage defects. Previous tissue engineering attempts using multipotent stem cells such as adult msenchymal stem cells or pluripotent stem cells such as embryonic stem cells were qualitative, variable and result in the formation of a tissue of a fibrocatilagenous phenotype. This study aims to identify the factors that control the differentiation of human induced pluripotent stem cells towards the chondrogenic lineage and to then assess their capacity to scale up and use in 3D cartilage tissue engineering. The hiPSC lines, C18 and C19, were shown to express pluripotent transcription factors OCT4 and Nanog by immunofluorescence and have the capacity to differentiate into the cells descended from the three germ layers. The pluripotent stem cells were directed to the chondrogenic lineage in a feeder-free and chemically defined system using a sequential addition of growth factors including Activin A, FGF-2 and BMP-4. The derived chondroprogenitors showed similar characteristics to genuine mesenchymal stem cells including adherence to plastic, fibroblastic morphology and expression of cell surface markers, except for the trilineage potential. The derived cells were seeded on 3D fibronectin coated PGA scaffolds and other biomaterials stimulated with TGF-p3 and BMP-7 resulting in a type IT collagen production reaching similar levels to previously reported levels with mesenchymal stem cells and a sGAG production of similar levels to native cartilage reaching 40% of dry weight.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652038 |
| Date | January 2014 |
| Creators | Owaidah, Amani Yousef |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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