Culture Adaptation in Human Embryonic Stem Cell Lines

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Human embryonic stem (ES) cells offer considerable opportunities for regenerative medicine, drug discovery and toxicology. To realise this potential, a detailed understanding of their basic biology is required. It has become evident over the past three to four years that human ES cells may undergo genetic and other changes that may enhance their capacity for growth in culture, when they are maintained for extended periods. We have called this process, ‘culture adaptation’. The underlying hypothesis of this proposal is that the mechanisms affected during culture adaptation of ES cells are those that control the balance between self renewal, differentiation and death of these pluripotent stem cells. Understanding the basis for adaptation may not only provide a rational basis for designing improved methods to culture these cells while minimising the appearance of variants, but also may provide insights into the processes that control the self renewal of pluripotent stem cells and suggest approaches for controlling their growth and differentiation. Further, an understanding of culture adaptation of ES cells may provide insights into the mechanisms that drive progression of teratocarcinomas, a rare tumour of young men, but also a paradigm for other stem cell based malignancies.