Generation of Functional Hepatocytes From Mouse Induced Pluripotent Stem Cells
Generation of Functional Hepatocytes From Mouse Induced Pluripotent Stem Cells
复制标题
从小鼠诱导多能干细胞生成功能性肝细胞
DOI：
10.1002/jcp.22000
复制
发表时间：
2010-03-01
影响因子：
5.6
通讯作者：
Xiang, Andy Peng
中科院分区：
文献类型：
--
作者：
Li, Weiqiang;Wang, Ding;Xiang, Andy Peng
诱导多能干细胞是由体细胞通过多种转录因子的强制表达而产生的。诱导多能干细胞在许多方面与胚胎干细胞相似，如某些干细胞标志物的表达、染色质甲基化模式、类胚体形成和畸胎瘤形成。因此，诱导多能干细胞为发育生物学研究提供了强有力的工具，为移植治疗提供了无限的资源。在此，我们成功地诱导了小鼠诱导的多能干细胞，并报道了一种简单有效的方法，即通过依次添加诱导因子，从小鼠诱导的多能干细胞分化为有功能的肝细胞。诱导的多能干细胞来源的肝细胞与小鼠胚胎干细胞来源的肝细胞一样，表达肝细胞系标志物CK7、CK8、CK18、CK19、甲胎蛋白、白蛋白、Cyp7a1，并表现出肝功能特性，包括糖原储存、吲哚青绿(ICG)摄取和释放、低密度脂蛋白(LDL)摄取和尿素分泌。虽然我们观察到诱导多能干细胞与普通小鼠胚胎干细胞在肝脏分化效率上有一定的差异，但我们的结果表明，小鼠诱导多能干细胞在体外可以有效地分化为有功能的肝细胞，这可能对肝脏发育和再生医学的研究有所帮助。J.细胞。物理。222：492-501,2010。(C)2009年Wiley-Liss，Inc.
Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine. J. Cell. Physiol. 222: 492-501, 2010. (C) 2009 Wiley-Liss, Inc.