Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes

Yong Chen, Yanfeng Li, Xia Wang, Wei Zhang, Vanessa Sauer, Chan Jung Chang, Bing Han, Tatyana Tchaikovskaya, Yesim Avsar, Edgar Tafaleng, Sanal Madhusudana Girija, Krisztina Tar, Zsuzsanna Polgar, Stephen Strom, Eric E. Bouhassira, Chandan Guha, Ira J. Fox, Jayanta Roy-Chowdhury, Namita Roy-Chowdhury

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Hepatocyte transplantation has the potential to cure inherited liver diseases, but its application is impeded by a scarcity of donor livers. Therefore, we explored whether transplantation of hepatocyte-like cells (iHeps) differentiated from human induced pluripotent stem cells (iPSCs) could ameliorate inherited liver diseases. iPSCs reprogrammed from human skin fibroblasts were differentiated to iHeps, which were transplanted into livers of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-deficient Gunn rats, a model of Crigler-Najjar syndrome 1 (CN1), where elevated unconjugated bilirubin causes brain injury and death. To promote iHep proliferation, 30% of the recipient liver was X-irradiated before transplantation, and hepatocyte growth factor was expressed. After transplantation, UGT1A1+ iHep clusters constituted 2.5%-7.5% of the preconditioned liver lobe. A decline of serum bilirubin by 30%-60% and biliary excretion of bilirubin glucuronides indicated that transplanted iHeps expressed UGT1A1 activity, a postnatal function of hepatocytes. Therefore, iHeps warrant further exploration as a renewable source of hepatocytes for treating inherited liver diseases.

Original languageEnglish (US)
Pages (from-to)22-30
Number of pages9
JournalStem Cell Reports
Volume5
Issue number1
DOIs
StatePublished - Jul 14 2015

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Chen, Y., Li, Y., Wang, X., Zhang, W., Sauer, V., Chang, C. J., Han, B., Tchaikovskaya, T., Avsar, Y., Tafaleng, E., Madhusudana Girija, S., Tar, K., Polgar, Z., Strom, S., Bouhassira, E. E., Guha, C., Fox, I. J., Roy-Chowdhury, J., & Roy-Chowdhury, N. (2015). Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes. Stem Cell Reports, 5(1), 22-30. https://doi.org/10.1016/j.stemcr.2015.04.017