Abstract
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.
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Acknowledgments
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).
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Polgar, Z., Li, Y., Li Wang, X., Guha, C., Roy-Chowdhury, N., Roy-Chowdhury, J. (2017). Gunn Rats as a Surrogate Model for Evaluation of Hepatocyte Transplantation-Based Therapies of Crigler–Najjar Syndrome Type 1. In: Stock, P., Christ, B. (eds) Hepatocyte Transplantation. Methods in Molecular Biology, vol 1506. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6506-9_9
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DOI: https://doi.org/10.1007/978-1-4939-6506-9_9
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