title: Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes.
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.
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sauer
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Tchaikovskaya
authors.affiliation: 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.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Avsar
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Tafaleng
authors.affiliation: 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.
authors.forename: Sanal
authors.initials: S
authors.lastname: Madhusudana Girija
authors.affiliation: 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.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Tar
authors.affiliation: 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.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Polgar
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Stephen
authors.initials: S
authors.lastname: Strom
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
authors.affiliation: 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.
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.affiliation: Department of Surgery and McGowan Institute for Regenerative Medicine, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Fox
authors.affiliation: 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.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Roy-Chowdhury
authors.affiliation: 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.
authors.forename: Namita
authors.initials: N
authors.lastname: Roy-Chowdhury
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood; D064987:Cell- and Tissue-Based Therapy; D003414:Crigler-Najjar Syndrome / Q000097:blood / Q000473:pathology / Q000628:therapy*; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000235:genetics / Q000628:therapy*; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D008099:Liver / Q000473:pathology / Q000601:surgery; D051381:Rats; D011911:Rats, Gunn; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; C499946:Ugt1a1 protein, rat; D000099148:UGT1A1 Enzyme