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Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.

ABSTRACT: Although embryonic stem (ES) cell-derived hepatocytes have the capacity for liver engraftment and repopulation, their in vivo hepatic function has not been analyzed yet. We aimed to determine the metabolic function and therapeutic action of ES cell-derived hepatocytes after serial liver repopulations in fumaryl acetoacetate hydrolase knockout (Fah(-/-)) mice. Albumin expressing (Alb(+)) cells were obtained by hepatic differentiation of ES cells using two frequently reported methods. After transplantation, variable levels of liver repopulation were found in Fah(-/-) mice recipients. FAH expressing (FAH(+)) hepatocytes were found either as single cells or as nodules with multiple hepatocytes. After serial transplantation, the proportion of the liver that was repopulated by the re-transplanted FAH(+) hepatocytes increased significantly. ES cell-derived FAH(+) hepatocytes were found in homogenous nodules and corrected the liver metabolic disorder of Fah(-/-) recipients and rescued them from death. ES cell-derived hepatocytes had normal karyotype, hepatocytic morphology and metabolic function both in vitro and in vivo. In conclusion, ES cell-derived hepatocytes were capable of liver repopulation and correction of metabolic defects after serial transplantation. Our results are an important piece of evidence to support future clinical applications of ES cell-derived hepatocytes in treating liver diseases.

SUBMITTER: He ZY

PROVIDER: S-EPMC3314493 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.

He Zhi-Ying ZY Deng Li L Li Yang-Fang YF Xiang Dao D Hu Jun-Kai JK Chen Yuan-Xiao YX Wang Min-Jun MJ Chen Fei F Liu Chang-Cheng CC Li Wen-Lin WL Zi Xiao-Yuan XY Wu Xia X Li Guang-Peng GP Wangensteen Kirk J KJ Hu Yi-Ping YP Wang Xin X

The international journal of biochemistry & cell biology 20120110 4

Although embryonic stem (ES) cell-derived hepatocytes have the capacity for liver engraftment and repopulation, their in vivo hepatic function has not been analyzed yet. We aimed to determine the metabolic function and therapeutic action of ES cell-derived hepatocytes after serial liver repopulations in fumaryl acetoacetate hydrolase knockout (Fah(-/-)) mice. Albumin expressing (Alb(+)) cells were obtained by hepatic differentiation of ES cells using two frequently reported methods. After transp ...[more]

PMID: 22249028

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Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.

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Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.

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