Myoblast transplantation: murine studies

Kathryn Pellegrini

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated abstract] Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterised by widespread muscle fibre necrosis followed by the replacement of muscle with connective and adipose tissue. The pathology of DMD is attributable to the absence of dystrophin, which is a structural protein essential for the stability of muscle. Myoblast transplantation is a cell-mediated gene replacement approach that utilises the natural repair mechanism of skeletal muscle to achieve dystrophin expression within muscle fibres with the aim of producing a significant clinical improvement in muscle strength. However, the efficacy of this approach has been limited by the poor survival rate of the injected myoblasts. Efforts to improve the efficacy of myoblast transplantation have focussed on immunological rejection and the low levels of donor myoblast migration within the recipient muscle. Additional research has also aimed to identify a more appropriate donor cell population and optimise the delivery of the donor cells. Therefore, the research presented within this thesis aimed to improve the in vivo survival of donor myoblasts by reviewing basic parameters of the myoblast transplantation procedure such as the use of immunodeficient mice, the number of cells transplanted and the induction of regeneration prior to transplantation. Attempts were also made to isolate satellite cells and myofibres for immediate transplantation and cultured myoblasts were transplanted adhered to artificial supports. The research presented in Chapter 4 investigated some potential causes of donor myoblast death following intramuscular transplantation. The effect of the immune system, the effect of variations in the number and density of the cells injected and attempts to improve the incorporation of donor myoblasts into the injection environment were all considered.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2011

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