AI Article Synopsis

  • Human induced pluripotent stem cells (iPSCs) have potential for generating liver cells for treating end-stage liver disease through a multistage differentiation protocol.
  • Research demonstrates that iPSC-derived hepatic cells can successfully engraft and regenerate liver tissue in mouse models, showing their functionality.
  • iPSCs from different developmental origins exhibit similar efficiency in differentiating into hepatic cells and can secrete human liver proteins effectively, indicating their promise for liver regeneration therapy.

Article 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 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305909PMC
http://dx.doi.org/10.1126/scitranslmed.3002376DOI Listing

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