Gunn Rats as a Surrogate Model for Evaluation of Hepatocyte Transplantation-Based Therapies of Crigler-Najjar Syndrome Type 1.
Liver transplantation has been established as a curative therapy for acute and chronic liver failure, as well as liver-based inherited metabolic diseases. Because of the complexity of organ transplantation and the worldwide shortage of donor organs, hepatocyte transplantation is being developed as a bridging therapy until donor organs become available, or for amelioration of inherited liver-based diseases. The Gunn rat is a molecular and metabolic model of Crigler-Najjar syndrome type 1, which is characterized by lifelong unconjugated hyperbilirubinemia due to the lack of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-mediated bilirubin glucuronidation. Gunn rats are convenient for evaluating the effect of hepatocyte transplantation or gene therapy, because the extent of UGT1A1 replacement can be assessed by serial determination of serum bilirubin levels, and excretion of bilirubin glucuronides in bile provide definitive evidence of the function of the transplanted hepatocytes or the effect of gene therapy. The core techniques involved in hepatocyte transplantation in Gunn rats are discussed in this chapter.
Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Zsuzsanna
Z
Polgar
Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Yanfeng
Y
Li
Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.|Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Xia
X
Li Wang
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Departments of Radiation Oncology and Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Chandan
C
Guha
Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. Namita.Roychowdhury@Einstein.YU.edu.|Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA. Namita.Roychowdhury@Einstein.YU.edu.|Department of Genetics, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Ullmann Building, Bronx, NY, USA. Namita.Roychowdhury@Einstein.YU.edu.
Namita
N
Roy-Chowdhury
Division of Gastroenterology and Liver Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA. Jayanta.Roy-Chowdhury@Einstein.YU.edu.|Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA. Jayanta.Roy-Chowdhury@Einstein.YU.edu.|Department of Genetics, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Ullmann Building, Bronx, NY, USA. Jayanta.Roy-Chowdhury@Einstein.YU.edu.
Jayanta
J
Roy-Chowdhury
D000818:Animals; D001646:Bile / Q000737:chemistry; D001654:Bile Pigments / Q000032:analysis; D001663:Bilirubin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods; D017690:Cell Transplantation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003414:Crigler-Najjar Syndrome / Q000097:blood / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism / Q000601:surgery*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D011911:Rats, Gunn; D000099148:UGT1A1 Enzyme
D001654:Bile Pigments; D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C016266:bilirubin glucuronate
Bile pigment analysis; Bilirubin; Crigler–Najjar syndrome; Gunn rats; Hepatocyte transplantation