Pouton Colin W, Haynes John M
Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Melbourne, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Adv Drug Deliv Rev. 2005 Dec 12;57(13):1918-34. doi: 10.1016/j.addr.2005.08.003. Epub 2005 Nov 9.
Embryonic stem cells (ESCs) will become a source of all adult differentiated cells once reliable protocols for directed differentiation have been established. This resource will revolutionise laboratory cell biology and will provide much improved cell culture models for discovery and development of drugs, and fundamental studies of the genetic basis of disease. These are early days, and there are few examples of practical outcomes in the pharmaceutical world, though in recent years some drug-like molecules, which direct differentiation, have been discovered. At this stage the focus is on understanding the signalling systems and transcription factors that drive differentiation, on characterisation and isolation of precursor cells, and on establishing methods to improve the homogeneity of differentiated cells derived from ESCs. There is particular interest in establishing methods for deriving fully differentiated human cells from human ESCs (HESCs), but there are challenges to be met before HESC technology can be taken up in a widespread manner. Protocols for expansion of HESC cultures are labour-intensive at present. There is an urgent need for discovery of factors that will allow serum-free (and feeder cell-free) expansion of HESCs, and which can be applied to the majority of HESC lines. Our expectation is that adequate protocols will emerge in the coming years opening the way for development of many cell culture tools in the pharmaceutical industry. Here we review the current status and future prospects for this exciting field and encourage pharmaceutical scientists to play a role in directing its development.
一旦建立了可靠的定向分化方案，胚胎干细胞（ESCs）将成为所有成体分化细胞的来源。这一资源将彻底改变实验室细胞生物学，并为药物发现与开发以及疾病遗传基础的基础研究提供大为改进的细胞培养模型。目前尚处于早期阶段，制药领域的实际成果实例较少，不过近年来已经发现了一些能够指导分化的类药物分子。现阶段的重点在于了解驱动分化的信号系统和转录因子，对前体细胞进行表征和分离，以及建立提高源自ESCs的分化细胞同质性的方法。人们尤其关注建立从人胚胎干细胞（HESCs）中获得完全分化的人类细胞的方法，但在HESC技术能够广泛应用之前仍有诸多挑战需要应对。目前，HESC培养的扩增方案需要耗费大量人力。迫切需要发现能够实现HESCs无血清（且无饲养层细胞）扩增的因子，并且这些因子能够应用于大多数HESC系。我们预计，未来几年将会出现合适的方案，为制药行业开发众多细胞培养工具开辟道路。在此，我们综述这一令人兴奋的领域的现状和未来前景，并鼓励制药科学家在引导其发展方面发挥作用。
