The effect of mechanical stimulation and biological factors on human mesenchymal stem cell and human articular cartilage progenitor cell chondrogenesis and hypertrophy

Neumann, Alexander J. 2013. The effect of mechanical stimulation and biological factors on human mesenchymal stem cell and human articular cartilage progenitor cell chondrogenesis and hypertrophy. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Adult articular cartilage has a limited repair capacity. This leads to an increasing demand for optimised repair techniques. Furthermore, current procedures to regenerate articular cartilage fail to achieve sufficient results. Previous work within our group suggested that combination of functional tissue engineering and gene transfer represents a promising alternative approach. In this thesis, different viral gene transfer methods were investigated and optimised. A clinically relevant three dimensional transduction model was developed. These results were directly implemented in further work aiming to investigate the combined effect of multiaxial mechanical stimulation and adenoviral-mediated over-expression of bone morphogenetic protein 2 on human chondroprogenitor cell chondrogenesis and progression towards hypertrophy. Two cell sources were investigated, namely human mesenchymal stem cells and human articular cartilage progenitor cells. The combined approached enhanced human mesenchymal stem cell chondrogenesis. Yet, it was not possible to completely prevent progression towards hypertrophy. For human articular cartilage progenitor cells, over-expression of bone morphogenetic protein 2 did enhance their chondrogenic differentiation potential. However, mechanical stimulation alone, in the absence of exogenous growth factors, led to stable chondrogenic induction without signs of hypertrophic differentiation. This suggests these cells should be further investigated. Additionally, the potential of Dorsomorphin, as possible agent to block hypertrophic differentiation by inhibition of bone morphogenetic protein signalling, was investigated in a fibrin polyurethane composite system, using human mesenchymal stem cells. As opposed to the pellet culture model, application of Dorsomorphin led to a cytotoxic effect which decreased the general differentiation potential. Finally, the chondrogenic potential of the two cell types was directly compared, using the pellet culture model. Under serum-free conditions, human articular cartilage progenitor cells were not able to undergo chondrogenesis. The reasons for this remain to be elucidated. The combined results of the thesis can help to develop a novel one-step procedure to treat articular cartilage defects.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords:	Tissue Engineering, Chondrogenesis, Hypertrophy, Mesenchymal stem cells, Mechanical stimulation, Gene transfer
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:21
URI:	https://orca.cardiff.ac.uk/id/eprint/48710

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