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Stem Cell Reports. 2015 Jul 14;5(1):22-30. doi: 10.1016/j.stemcr.2015.04.017. Epub 2015 Jun 11.

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

Author information

1
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Departments of Radiation Oncology and Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
3
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4
Department of Surgery and McGowan Institute for Regenerative Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
5
Department of Laboratory Medicine, Karolinska Institute, 17177 Stockholm, Sweden.
6
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: jayanta.roy-chowdhury@einstein.yu.edu.
7
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: namita.roychowdhury@einstein.yu.edu.

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.

PMID:
26074313
PMCID:
PMC4618248
DOI:
10.1016/j.stemcr.2015.04.017
[Indexed for MEDLINE]
Free PMC Article

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