Sauer Vanessa, Roy-Chowdhury Namita, Guha Chandan, Roy-Chowdhury Jayanta
Department of Medicine (Division of Gastroenterology and Hepatology), Albert Einstein College of Medicine, New York ; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York.
Department of Medicine (Division of Gastroenterology and Hepatology), Albert Einstein College of Medicine, New York ; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York ; Department of Genetics, Albert Einstein College of Medicine, New York.
Curr Pathobiol Rep. 2014 Mar;2(1):11-20. doi: 10.1007/s40139-013-0039-2.
During the past decade, a series of discoveries has established the potential of the so called terminally differentiated cells to transition to more primitive progenitor cells. The dramatic demonstration of the ability to reprogram differentiated somatic cells to induced pluripotent stem cells (iPSC) that can then give rise to cells of all three germ layers has opened the possibility of generating virtually any cell type in culture, from any given individual. Taking advantage of these concepts, researchers have generated iPSCs by reprogramming a wide variety of somatic cells. In addition to their practical implications, these studies have provided crucial insights into the mechanism of cell plasticity that underlies the transition from one cell type to another. Using concepts derived from research on embryological development, investigators have differentiated iPSCs to cells resembling hepatocytes in many ways. Such hepatocyte-like cells could be of enormous value in disease modeling, drug discovery and regenerative medicine. However, the currently available methods do not yield cells that fully reproduce the characteristics of adult primary hepatocytes. Thus generating hepatocytes from iPSCs is very much a work in progress. In addition to chronicling these exciting developments, this review will discuss the emergent new approaches to generating iPSCs, improving their differentiation to hepatocyte-like cells and maintaining the hepatocyte-like cells in culture for longer survival and better function.
在过去十年中，一系列发现证实了所谓终末分化细胞转变为更原始祖细胞的潜力。将分化的体细胞重编程为诱导多能干细胞（iPSC），进而产生所有三个胚层细胞的能力得到了显著证明，这使得从任何给定个体在培养中生成几乎任何细胞类型成为可能。利用这些概念，研究人员通过对多种体细胞进行重编程生成了iPSC。除了具有实际意义外，这些研究还为细胞可塑性机制提供了关键见解，而细胞可塑性是细胞从一种类型转变为另一种类型的基础。研究人员利用胚胎发育研究中得出的概念，已将iPSC在许多方面分化为类似肝细胞的细胞。这种类肝细胞在疾病建模、药物发现和再生医学中可能具有巨大价值。然而，目前可用的方法无法产生完全重现成年原代肝细胞特征的细胞。因此，从iPSC生成肝细胞仍有很长的路要走。除了记录这些令人兴奋的进展外，本综述还将讨论生成iPSC、改善其向类肝细胞分化以及在培养中维持类肝细胞更长存活时间和更好功能的新出现方法。
