In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins.
In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins.
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DOI：
10.1126/scitranslmed.3002376
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发表时间：
2011-05-11
影响因子：
17.1
通讯作者：
Jang YY
中科院分区：
文献类型：
--
作者：
Liu H;Kim Y;Sharkis S;Marchionni L;Jang YY
人诱导多能干细胞(IPSCs)是肝移植治疗终末期肝病的潜在肝细胞来源。使用多阶段分化方案已在体外将人IPSCs分化为肝细胞，但这些细胞是否具有功能以及是否有能力移植和再生病变肝组织尚不清楚。我们证明了不同分化阶段的人IPSC来源的肝细胞可以在小鼠移植模型中植入肝脏。使用相同的分化和移植方案，我们还评估了来自三个发育生殖层组织(即外胚层、中胚层和内胚层)的人IPSCs再生小鼠肝脏的能力。这些IPSC株具有相似但不同的全球DNA甲基化模式，以类似于人类胚胎干细胞的效率分化为多阶段肝细胞。从不同来源的IPSC系分离的不同分化阶段的人肝细胞成功地在肝硬变小鼠的肝组织中再生。他们还将人类特有的肝脏蛋白分泌到小鼠血液中，其浓度与人类初级肝细胞分泌的蛋白质浓度相当。我们的结果证实了人IPSC来源的多阶段肝细胞在体内的植入和肝再生能力，并表明不同来源的人IPSC可以有效地沿着肝脏谱系分化，而不考虑其父母的表观遗传记忆。
Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stage liver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiation protocol, but whether these cells are functional and capable of engrafting and regenerating diseased liver tissue is not clear. We show that human iPSC-derived hepatic cells at various differentiation stages can engraft the liver in a mouse transplantation model. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived from each of the three developmental germ layer tissues (that is, ectoderm, mesoderm, and endoderm) to regenerate mouse liver. These iPSC lines, with similar but distinct global DNA methylation patterns, differentiated into multistage hepatic cells with an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derived from iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secreted human-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primary hepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistage hepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memory can efficiently differentiate along the hepatic lineage.
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影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
3.7
作者：
Marchetto MC;Yeo GW;Kainohana O;Marsala M;Gage FH;Muotri AR
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12.3
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Zhang J
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14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
影响因子：
11.2
作者：
Daniel VC;Marchionni L;Hierman JS;Rhodes JT;Devereux WL;Rudin CM;Yung R;Parmigiani G;Dorsch M;Peacock CD;Watkins DN
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Watkins DN