Culture Adaptation in Human Embryonic Stem Cell Lines

人类胚胎干细胞为再生医学、药物发现和毒理学提供了相当大的机会。为了实现这一潜力，需要详细了解它们的基本生物学。在过去的三到四年里，很明显，人类胚胎干细胞可能会发生遗传和其他变化，当它们被长期保存时，这些变化可能会增强它们在培养物中的生长能力。我们把这个过程称为“文化适应”。这一提议的基本假设是，在胚胎干细胞培养适应过程中受影响的机制是那些控制这些多能干细胞自我更新、分化和死亡之间平衡的机制。了解适应的基础不仅可以为设计改进的培养这些细胞的方法提供合理的基础，同时最大限度地减少变异的出现，而且还可以为控制多能干细胞自我更新的过程提供见解，并提出控制其生长和分化的方法。此外，对胚胎干细胞的培养适应性的理解可能为驱动畸胎癌（一种罕见的年轻男性肿瘤）进展的机制提供见解，同时也为其他基于干细胞的恶性肿瘤提供范例。

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.