In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins

Hua Liu, Yonghak Kim, Saul Sharkis, Luigi Marchionni, Yoon Young Jang

Research output: Contribution to journalArticle

Abstract

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 multi-stage 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.

Original languageEnglish (US)
Article number82ra39
JournalScience Translational Medicine
Volume3
Issue number82
DOIs
StatePublished - May 11 2011

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Induced Pluripotent Stem Cells
Liver Regeneration
Hepatocytes
Liver
Transplantation
Cell Line
Germ Layers
Endoderm
Ectoderm
End Stage Liver Disease
Aptitude
Mesoderm
DNA Methylation
Epigenomics
Liver Cirrhosis
Liver Transplantation
Liver Diseases
Proteins
Efficiency

ASJC Scopus subject areas

  • Medicine(all)

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In vivo liver regeneration potential of human induced pluripotent stem cells from diverse origins. / Liu, Hua; Kim, Yonghak; Sharkis, Saul; Marchionni, Luigi; Jang, Yoon Young.

In: Science Translational Medicine, Vol. 3, No. 82, 82ra39, 11.05.2011.

Research output: Contribution to journalArticle

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