Neal, A; (2013) Satellite Cell Subpopulations and Environmental Mediators of their Function: Implications for Stem Cell Therapy in Skeletal Muscle. Doctoral thesis , UCL (University College London).

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Abstract

Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre (myofibre). Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. There is a need to investigate factors that enable satellite cell survival and/or proliferation post engraftment in order to obtain the optimal donor cell and host environment for efficient satellite cell transplantation. I have investigated sex differences in mouse satellite cell populations across the lifespan in vitro and in vivo. I show that satellite cell number and myogenic regulator factor expressions differ according to sex and developmental stage. Despite this, I show that engraftment efficiency is not mediated by the age or sex of the host or the donor. I hypothesise that there are two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. I have used high doses of ionising radiation to separate radio-resistant from radio-sensitive satellite cells. I demonstrate that radio resistant satellite cells do not contribute to growth, but are able to contribute to host muscle regeneration post transplantation and have compared their expression pro files using microarray. I hypothesise that satellite cells able to survive high dose ionizing radiation are the same population of satellite cells that are able to survive transplantation. Engraftment efficiency is greatly improved if host muscle is exposed to ionizing radiation prior to engraftment. I demonstrate that elimination of the host satellite cell pool is not sufficient to account for the improved engraftment efficiency with radiation and I have therefore investigated the role of the vasculature as a mediator of radiation induced improvement in engraftment efficiency.

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