Goldberg, Andrew Julian; (2006) Use of human autologous chondrocytes and mesenchymal progenitor cells in cartilage repair techniques. Doctoral thesis , UCL (University College London).

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Abstract

Due to articular cartilage's limited intrinsic repair potential, the treatment of cartilage damage in the younger patient provides a major challenge. The relative failure of many synthetic solutions, has led to the growing interest in the development of cell-based repair systems. In general two strategies have been considered. The first approach is to enhance the intrinsic healing capacity of both the cartilage and subchondral bone through the release of mesenchymal progenitor cells, however, to date, these techniques have only led to fibrocartilaginous repairs, which lack long term durability. An alternative approach involves the use of tissue engineering strategies to elicit a biological repair. The most commonly used practice in the clinical setting is Autologous Chondrocyte Implantation (ACI). This thesis presents a review of the literature in the subject of cartilage repair, looks at the cell sources available to develop repair systems and investigates factors that might influence these cells. In this study, an in vitro system was used to promote the chondrogenic potential of these cells allowing for study of some of the factors responsible for this complex process. Human mesenchymal progenitor cells were isolated by self selection through monolayer culture and induced to chondrogenic differentiation in a pellet model using culture in a chemically defined serum-free medium. The effects of dynamic compression on freshly isolated and passaged human chondrocytes was also studied. Results suggest that a defined medium, containing TGFp, is necessary to induce the re-expression of a differentiated chondrocyte phenotype and the subsequent stimulation of GAG and type II collagen. This thesis highlights a number of areas where knowledge could be improved in relation to the biomechanical events that take place in the repair of cartilage defects and a theory is proposed to explain why marrow techniques lead to a fibrocartilage repair. Andrew Julian Goldberg 2006 Interdisciplinary Research Centre, Institute of Orthopaedics, Royal Free & University College Medical School, London, UK. Medical Engineering Division and IRC in Biomedical Materials, Department of Engineering, Queen Mary, University of London, Mile End Road London, E1 4NS. Submitted in fulfillment of the requirements for the degree of MD.

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