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

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 ameliora...

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Main Authors:	Chen, Yong, Li, Yanfeng, Wang, Xia, Zhang, Wei, Sauer, Vanessa, Chang, Chan-Jung, Han, Bing, Tchaikovskaya, Tatyana, Avsar, Yesim, Tafaleng, Edgar, Madhusudana Girija, Sanal, Tar, Krisztina, Polgar, Zsuzsanna, Strom, Stephen, Bouhassira, Eric E., Guha, Chandan, Fox, Ira J., Roy-Chowdhury, Jayanta, Roy-Chowdhury, Namita
Format:	Online
Language:	English
Published:	Elsevier 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618248/

id	pubmed-4618248
recordtype	oai_dc
spelling	pubmed-46182482015-11-24 Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes Chen, Yong Li, Yanfeng Wang, Xia Zhang, Wei Sauer, Vanessa Chang, Chan-Jung Han, Bing Tchaikovskaya, Tatyana Avsar, Yesim Tafaleng, Edgar Madhusudana Girija, Sanal Tar, Krisztina Polgar, Zsuzsanna Strom, Stephen Bouhassira, Eric E. Guha, Chandan Fox, Ira J. Roy-Chowdhury, Jayanta Roy-Chowdhury, Namita Report 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. Elsevier 2015-06-11 /pmc/articles/PMC4618248/ /pubmed/26074313 http://dx.doi.org/10.1016/j.stemcr.2015.04.017 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Yong Li, Yanfeng Wang, Xia Zhang, Wei Sauer, Vanessa Chang, Chan-Jung Han, Bing Tchaikovskaya, Tatyana Avsar, Yesim Tafaleng, Edgar Madhusudana Girija, Sanal Tar, Krisztina Polgar, Zsuzsanna Strom, Stephen Bouhassira, Eric E. Guha, Chandan Fox, Ira J. Roy-Chowdhury, Jayanta Roy-Chowdhury, Namita
spellingShingle	Chen, Yong Li, Yanfeng Wang, Xia Zhang, Wei Sauer, Vanessa Chang, Chan-Jung Han, Bing Tchaikovskaya, Tatyana Avsar, Yesim Tafaleng, Edgar Madhusudana Girija, Sanal Tar, Krisztina Polgar, Zsuzsanna Strom, Stephen Bouhassira, Eric E. Guha, Chandan Fox, Ira J. Roy-Chowdhury, Jayanta Roy-Chowdhury, Namita Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
author_facet	Chen, Yong Li, Yanfeng Wang, Xia Zhang, Wei Sauer, Vanessa Chang, Chan-Jung Han, Bing Tchaikovskaya, Tatyana Avsar, Yesim Tafaleng, Edgar Madhusudana Girija, Sanal Tar, Krisztina Polgar, Zsuzsanna Strom, Stephen Bouhassira, Eric E. Guha, Chandan Fox, Ira J. Roy-Chowdhury, Jayanta Roy-Chowdhury, Namita
author_sort	Chen, Yong
title	Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
title_short	Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
title_full	Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
title_fullStr	Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
title_full_unstemmed	Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes
title_sort	amelioration of hyperbilirubinemia in gunn rats after transplantation of human induced pluripotent stem cell-derived hepatocytes
description	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.
publisher	Elsevier
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618248/
_version_	1613492082425462784

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

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