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Effets à long terme de la transplantation hépatocytaire sur la carcinogenèse hépatique chez le rat Long-Evans Cinnamon /
| Content Provider | Semantic Scholar |
|---|---|
| Author | Beaudin, Marianne |
| Copyright Year | 2008 |
| Abstract | Introduction: The Long-Evans Cinnamon (LEC) rat is an animal model of Wilson's disease, an autosomal recessively inherited disorder caused by a mutation in the A TP7B gene. These rats bear the same mutation in the Atp7b gene and suffer spontaneous hepatitis that evolves to chronic hepatitis and eventualIy, hepatocellular carcinoma (HCC) and choiangiocellular carcinoma (CCC). Hepatocyte transplantation (HT) in LEC rats was performed to evaluate whether HT can prevent the development of liver tumor. Methods: LEC-HT rats (n=20) received 1/3 partial hepatectomy and HT from donor Long-Evans rats at 8 weeks of age. Immunosuppression was maintained with intra-peritoneal injections of Tacrolimus for 12 months. Control LEC rats (n=12) received only 1/3 partial hepatectomy. At 18 months of age, rats were sacrificed and liver was harvested for histology, donor cell engraftment by immunostaining for ATP7B and RT-PCR for Atp7b mRNA. Pre-neoplastic lesions ofHCC were confirmed by immunostaining for GST-1t. Results: Both HT rats and non-HT controls recovered from acute hepatitis, but showed persistent elevation of serum aminotransferases until sacrifice at 18 months of age. The survival before sacrifice was similar in both groups. Less HT rats developed HCC than controls (5% vs. 42%). AlI controls but one developed CCC (92%), whereas 13 out of 20 HT rats developed CCC (65%). Liver tissue expressed low levels of Atp7b mRNA (1.9±0.6%) in 4 out of 15 HT rats. AlI 4 rats expressing detectable Atp7b mRNA developed only hyperplastic nodules. ATP7Bpositive foci confirmed by immunohistochemistry were se en in the se 4 rats. AlI rats showed GST -1t positive modules and cholangiolar proliferation and fibrosis in non-tumoral tissues. Conclusions: HT, even at low repopulation rats, may delay the development of liver tumors in LEC rats. The presence of pre-neoplastic lesions in non-tumoral tissues suggests that development of liver tumors could not be prevented completely. Studies using strategies to increase donor cell engraftment are needed. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/7583/Beaudin_Marianne_2008_memoire.pdf?isAllowed=y&sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
