Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy
Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy
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DOI：
10.2174/1566523211313020006
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Dubart-Kupperschmitt, Anne
中科院分区：
文献类型：
--
作者：
Dianat, Noushin;Steichen, Clara;Dubart-Kupperschmitt, Anne
肝脏受到许多类型的疾病的影响，包括代谢紊乱和急性肝功能衰竭。原位肝移植（奥尔特）是目前唯一有效的治疗危及生命的肝脏疾病的方法，但同种异体肝细胞移植现在已成为一种替代方法，因为它比奥尔特侵入性更小，并且可以重复进行。然而，这种方法受到器官供体短缺以及与高质量成体肝细胞的分离、它们的冷冻保存和它们在培养中缺乏增殖相关的问题的阻碍。肝脏也是评估外源性药物的药代动力学和毒理学以及药物发现的关键器官，但缺乏合适的细胞培养系统。所有这些问题都突出了探索其他细胞来源的需要，例如可以分离、扩增以产生足够大的群体然后诱导分化成功能性肝细胞的干细胞。最近已经证实在正常肝脏中存在“兼性”祖细胞和干细胞的小生境，但它们不显示端粒酶活性。最近发现，人类诱导多能干细胞可以从体细胞中产生，这为再生医学和体外疾病建模带来了新的希望，因为这些细胞很容易获得。本文综述了目前从人多能干细胞诱导功能性肝细胞的研究进展、局限性和挑战，并展望了其在再生医学和药物开发中的应用前景。
The liver is affected by many types of diseases, including metabolic disorders and acute liver failure. Orthotopic liver transplantation (OLT) is currently the only effective treatment for life-threatening liver diseases but transplantation of allogeneic hepatocytes has now become an alternative as it is less invasive than OLT and can be performed repeatedly. However, this approach is hampered by the shortage of organ donors, and the problems related to the isolation of high quality adult hepatocytes, their cryopreservation and their absence of proliferation in culture. Liver is also a key organ to assess the pharmacokinetics and toxicology of xenobiotics and for drug discovery, but appropriate cell culture systems are lacking. All these problems have highlighted the need to explore other sources of cells such as stem cells that could be isolated, expanded to yield sufficiently large populations and then induced to differentiate into functional hepatocytes. The presence of a niche of "facultative" progenitor and stem cells in the normal liver has recently been confirmed but they display no telomerase activity. The recent discovery that human induced pluripotent stem cells can be generated from somatic cells has renewed hopes for regenerative medicine and in vitro disease modelling, as these cells are easily accessible. We review here the present progresses, limits and challenges for the generation of functional hepatocytes from human pluripotent stem cells in view of their potential use in regenerative medicine and drug discovery.