来源于人类诱导多能干细胞（人iPS细胞）的肝细胞是药物和细胞治疗空前的资源。但是，在体外由人类诱导多能干细胞定向分化成成熟的肝细胞仍然是具有挑战性的。迄今的研究很少注意到那些用于肝细胞分化的hiPSC细胞系间的差异。在本研究中，我们发展了一种改良的肝细胞分化的流程，比较了不同体细胞来源及应用不同载体如逆转录病毒、仙台病毒或附着体质粒所得的28种hiPSC细胞系。结果显示，细胞来源而不是方法，是影响肝细胞分化差异的重要因素。来源于外周血的hiPSC细胞系具有持续的高分化效率而来自成人真皮成纤维细胞的细胞系则分化效率低。然而，当对来自同一个体的外周血及真皮成纤维细胞的hiPSC进行比较时，我们发现肝细胞分化的差异很大程度上归结于个体的差异而不是细胞的来源。这些数据强调了在比较不同hiPSC 细胞系的分化能力时个体差异的重要性。
 

吉林大学第一医院肝胆胰内科 温晓玉 摘译
本文首次发表于[Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12538-12543]
 

Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells

Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation effciency, whereas many hiPSC clones from adult dermal broblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal broblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.