The aim of the present study was to analyse, retrospectively on a large panel of patients (149), the influence of the donor liver characteristics on the outcome of human hepatocyte isolation obtained from resected liver biopsies from surgical waste after hepatectomy. Among the pre-operative parameters, the type of disease, age and sex of the patient, previous chemotherapy, alcohol or tobacco consumption did not affect the yield, viability, attachment rate and function of the isolated human hepatocytes. Pre-operative biological and anatomopathological data indicated that, while mild steatosis (=10% steatotic hepatocytes) did also not affect the outcome of hepatocyte isolation, stronger steatosis (>10% steatotic hepatocytes) tended to decrease hepatocyte yield. Cholestasis, as assessed by gamma-glutamyl transferase serum values, significantly negatively correlated with the percentage of digested liver and the yield of viable cells. Intra-operative clamping time, that is, warm ischaemia, longer than 30 min was found to decrease both the percentage of digested liver and cell yield. Among the post-operative parameters, the percentage of digested liver decreased when biopsy weights were higher than 100 g, the use of glue tended to increase both the percentage of digested tissue and the yield of viable cells.In conclusion, human diseased livers appear to be a valuable source of isolated functional human hepatocytes. We recommend, for an optimal isolation, to use liver biopsies weighing less than 100 g, to glue the section surfaces of the biopsies and to avoid the use of moderate steatotic livers (>10% steatotic hepatocytes) and cholestatic livers, as well as livers undergoing warm ischaemia or clamping during resection due to the decrease in cell yield.
SummaryRepeated administration of thioacetam ide (TA), either intraperitoneally or in drinking water, produced liver cirrhosis in normal Sprague-Dawley rats (SDR ) with signi®cant histological alterations similar to those observed in human cirrhosis. In the present study, we evaluated the ability of TA to induce liver cirrhosis in mutant Nagase analbum inaemic SDR.T hioacetamide was administered either intraperitoneally up to 4 months or in drinking water up to 6 months to normal and to Nagase analbum inaemic SDR. Nagase analbum inaemic rat s (NAR ) were also administered TA in drinking water up to 10 months. Liver cirrhosis development was determined by macroscopic and microscopic analysis.In contrast to normal SDR, no histological characteristics of cirrhosis could be observed in NAR submitted to a 4 or 6 months treatm ent with TA. Such failure to induce cirrhosis in Nagase rats was con®rmed even after prolonged TA administrati on in drinking water for up to 10 months. In contrast, ®brosis and cholangiolar proliferation occurred in the 10-m onth TAtreated analbum inaem ic rats, suggesting that the mechanisms involved in cirrhosis induction are different from those involved in ®brosis development and carcinogenesis. It is unlikely that the protective effect against TA-induced cirrhosis observed in analbum inaemic rats is related to the absence of albumin in this rat strain, since a co-administration of TA with album in in analbum inaem ic rats did not restore the potential for TA to induce cirrhosis in this rat strain.In conclusion, the fact that induction of cirrhosis by TA is prevented in the inherently hyperlipidaem ic and hypercholesterolaemic analbum inaemic rats could be considered for potential applicati on in the treatm ent of clinical cirrhosis.
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