TY - CHAP
T1 - Gunn rats as a surrogate model for evaluation of hepatocyte transplantation-based therapies of crigler-najjar syndrome type 1
AU - Polgar, Zsuzsanna
AU - Li, Yanfeng
AU - Li Wang, Xia
AU - Guha, Chandan
AU - Roy-Chowdhury, Namita
AU - Roy-Chowdhury, Jayanta
N1 - Funding Information:
This work was supported in part by grants NIH RO1 1RO1 DK092469-01 (NR-C); NYSTEM CO24346 and CO26440 (JR-C); NIH 1PO1 DK 096990-01 (IJF and JR-C); and NIH P30 DK 41296-26 (Liver Pathobiology and Gene Therapy Research Core Center).
Publisher Copyright:
© Springer Science+Business Media New York 2017.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Bile pigment analysis
KW - Bilirubin
KW - Crigler-najjar syndrome
KW - Gunn rats
KW - Hepatocyte transplantation
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U2 - 10.1007/978-1-4939-6506-9_9
DO - 10.1007/978-1-4939-6506-9_9
M3 - Chapter
C2 - 27830550
AN - SCOPUS:84995503628
T3 - Methods in Molecular Biology
SP - 131
EP - 147
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -