胚胎干细胞分化为肝细胞的研究进展

Advances in the Research of Differentiation of Embryonic Stem Cells into Hepatocytes

目前 ,细胞移植作为终末期肝病的辅助治疗方法 ,移植的细胞必须满足在受体肝脏中存活、增殖并可分化为成熟肝细胞两个重要条件 ,但目前应用的肝细胞来源有限 ,其功能随着培养时间的延长而逐渐下降等问题限制了这一治疗策略的广泛开展。作为具有发育全能性和无限增殖能力的细胞 ,胚胎干细胞向肝细胞的分化研究近年来引起了广泛的关注 ,并取得了较大的进展 ,寻找合适、高效的分化诱导方法是目前研究的热点之一。胚胎干细胞向肝细胞的分化研究既可以为临床细胞替代治疗提供合适的细胞来源 ,也可以在药物评估和肝脏发育分化基础研究方面起到重要的作用。通过概括肝脏和拟胚体分化发育的分子机制 ,对体外胚胎干细胞向肝细胞分化的几种诱导体系作了介绍 ,并对分化肝细胞的应用前景和存在的问题进行了讨论。

Orthotopic liver transplantation has proven to be effective in the treatment of a variety of life-threatening liver diseases, however, the limitations of donated organs available and long-term immunosuppression provided an impetus for developing alternative therapies. Cell replacement strategies have been one major effective approach for overcoming the obstacles of organ transplantation in recent years. The exogenous cells should be able to proliferate and differentiate into mature hepatic cells after grafting. Use of mature hepatocytes is also hampered by limited tissue source and inability to proliferate and maintain the function for a long term in vitro. Embryonic stem cells are immortal and pluripotent and may provide a novel cell source for potential cell therapy. This review summarizes the mechanisms of controlling early liver development and hepatic differentiation of visceral endoderm in embryoid bodies, and provides an overview of diverse differentiation systems in vitro and in vivo that were applied to hepatic research in recent years. Several studies have demonstrated that ES cell-derived hepatocytes can incorporate into liver tissue and function in vivo, but a few of them have shown complete restoration of liver function after transplantation into mice with liver diseases. Further studies should be made to exploit efficient methods and clinical applications of hepatocytes derived from ES cells in the future. In addition to clinical transplantation for treatment of liver diseases, ES cells can provide a valuable tool for drug discovery applications and study on of molecular basis of hepatic differentiation.