Repopulation by endogenous hepatocytes does not reconstitute liver mass in rats treated with retrorsine.
The retrorsine (RS)-based model for massive liver repopulation was laid on the hypothesis that transplanted cells can proliferate in the recipient liver if the growth capacity of endogenous hepatocytes is persistently impaired. In order to directly test this hypothesis, we examined the long-term response to 2/3 partial hepatectomy (PH) in rats pretreated with RS, according to the protocol for liver repopulation. Rats were given RS or saline and 4 weeks later they underwent PH; they were killed up to 16 weeks thereafter. Liver weights, liver DNA, and protein content were significantly lower in the RS group throughout the experimental time considered (e.g., at 16 weeks post-PH relative liver weight was 1.99 +/- 0.30% in RS group vs. 3.06 +/- 0.5% in controls). Regenerative nodules were present in RS-treated livers; they occupied about 3% of the liver at 2 weeks post-PH and this value increased to nearly 50% at 8 weeks and to > 95% at 16 weeks. In conclusion, RS-treated rat liver is unable to recover its original mass for several months following PH, despite the development of regenerative nodules. This long-lasting effect is likely to contribute to the growth of transplanted hepatocytes, leading to massive liver repopulation.
Department of Biomedical Sciences and Biotechnology, Section of Experimental Pathology, University of Cagliari, Cagliari, Italy.
Sergio
S
Laconi
Silvia
S
Doratiotto
Stefania
S
Montisci
Paolo
P
Pani
Ezio
E
Laconi
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D004247:DNA / Q000032:analysis; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000033:anatomy & histology*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011763:Pyrrolizidine Alkaloids / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D000972:Antineoplastic Agents, Phytogenic; D018809:Proliferating Cell Nuclear Antigen; D011763:Pyrrolizidine Alkaloids; D019938:Cyclin D1; D004247:DNA; C003300:retrorsine