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Cell Transplant. 2013 Jun 13. [Epub ahead of print]

Preoperative hepatocyte transplantation improves the survival of rats with non -alcoholic steatohepatitis-related cirrhosis after partial hepatectomy.

Abstract

Objectives: Liver failure after liver resection for cirrhosis is a critical problem, and no effective therapy except liver transplantation is currently available. The objective of this study was to examine whether hepatocyte transplantation (HT) reduces the post-standard liver resection mortality rate of rats with non-alcoholic steatohepatitis (NASH)-related cirrhosis. Background: Liver resection for hepatocellular carcinoma (HCC) combined with NASH -related cirrhosis has become increasingly common. We developed a rat model of acute liver failure after 2/3 partial hepatectomy (PH) for NASH -related cirrhosis. The mechanism by which HT improved the survival of the model rats was examined in short - and long -term investigations. Methods: Male F344 with dipeptidyl peptidase IV (DPPIV)⁺ rats were used as donors, and female F344 DPPIV⁻ rats were used as recipients. The DPPIV⁻ recipient rats were fed the choline -deficient l -amino acid defined diet (CDAA) for 12 weeks. Some of the rats were transplanted with DPPIV⁺ hepatocytes 24 hours before undergoing PH, whereas others were not. The overall post -PH survival of each group was evaluated, and short - and long - term pathological and molecular biological evaluations were also performed. Then, the results of the HT and non-HT groups were compared. Results: Overall survival was significantly longer in the HT group than the non-HT group (7 -day survival rates: 46.7% and 7.7%, respectively). Compared with the recipient livers of the non-HT group, numerous Ki67⁺ hepatocytes and few TUNEL⁺ hepatocytes were observed in the livers of the HT group. At 6 months after the HT, the DPPIV⁺ hepatocytes had partially replaced the recipient liver and formed hepatocyte clusters in the spleen. Conclusions: Preoperative HT might improve the survival of rats with NASH -related cirrhosis after PH by preventing the host hepatocytes from accelerating their growth and falling into apoptosis.

PMID:
23768738
[PubMed - as supplied by publisher]
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