Immortalized common marmoset () hepatic progenitor cells possess bipotentiality in vitro and in vivo.

Zhenglong Guo, Renwei Jing, Quan Rao, Ludi Zhang, Yimeng Gao, Fengyong Liu, Xin Wang, Lijian Hui, HaiFang Yin
Author Information
  1. Zhenglong Guo: 1Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070 China.
  2. Renwei Jing: 1Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070 China.
  3. Quan Rao: 1Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070 China.
  4. Ludi Zhang: 2State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
  5. Yimeng Gao: 2State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
  6. Fengyong Liu: 3Department of Laboratory Animal, Tianjin Medical University, Tianjin, 300070 China.
  7. Xin Wang: 4Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Hohhot, 010021 China.
  8. Lijian Hui: 2State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
  9. HaiFang Yin: 1Department of Cell Biology, Tianjin Medical University, Qixiangtai Road, Heping District, Tianjin, 300070 China.

Abstract

Common marmoset () is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase ()-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.

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