Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease

Allen, Katrina J., Cheah, Daphne M. Y., Wright, Paul F. A., Gazeas, Sophie, Pettigrew-Buck, Nicole E., Deal, Yolanda H., Mercer, Julian and Williamson, Robert 2004, Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease, Journal of gastroenterology and hepatology, vol. 19, no. 11, pp. 1283-1290, doi: 10.1111/j.1440-1746.2004.03451.x.

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Title Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease
Author(s) Allen, Katrina J.
Cheah, Daphne M. Y.
Wright, Paul F. A.
Gazeas, Sophie
Pettigrew-Buck, Nicole E.
Deal, Yolanda H.
Mercer, Julian
Williamson, Robert
Journal name Journal of gastroenterology and hepatology
Volume number 19
Issue number 11
Start page 1283
End page 1290
Publisher Wiley Interscience
Place of publication New York, NY.
Publication date 2004
ISSN 0815-9319
Keyword(s) copper
liver cell therapy
toxic milk mouse
Wilson's disease
Summary Background and Aim: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.

Methods: Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.

Results: Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non-repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.

Conclusion: Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.

Language eng
DOI 10.1111/j.1440-1746.2004.03451.x
Field of Research 110307 Gastroenterology and Hepatology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©1999-2008, John Wiley & Sons, Inc.
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Document type: Journal Article
Collection: School of Biological and Chemical Sciences
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