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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
Human induced pluripotent stem cells (iPSCs) are a potential source of hepatocytes for liver transplantation to treat end-stageliver disease. In vitro differentiation of human iPSCs into hepatic cells has been achieved using a multistage differentiationprotocol, 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 transplantationmodel. Using the same differentiation and transplantation protocols, we also assessed the ability of human iPSCs derived fromeach 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 cellswith an efficiency similar to that of human embryonic stem cells. Human hepatic cells at various differentiation stages derivedfrom iPSC lines of different origins successfully repopulated the liver tissue of mice with liver cirrhosis. They also secretedhuman-specific liver proteins into mouse blood at concentrations comparable to that of proteins secreted by human primaryhepatocytes. Our results demonstrate the engraftment and liver regenerative capabilities of human iPSC-derived multistagehepatic cells in vivo and suggest that human iPSCs of distinct origins and regardless of their parental epigenetic memorycan efficiently differentiate along the hepatic lineage.
