title: 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.
authors.affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Yang-Fang
authors.initials: YF
authors.lastname: Li
authors.forename: Dao
authors.initials: D
authors.lastname: Xiang
authors.forename: Jun-Kai
authors.initials: JK
authors.lastname: Hu
authors.forename: Yuan-Xiao
authors.initials: YX
authors.lastname: Chen
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Liu
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Li
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Zi
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.forename: Guang-Peng
authors.initials: GP
authors.lastname: Li
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: Wangensteen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006867:Hydrolases / Q000172:deficiency; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors
chemical_list: D000418:Albumins; D006867:Hydrolases; C020156:fumarylacetoacetase