title: N-acetylcysteine improves the viability of human hepatocytes isolated from severely steatotic donor liver tissue.
abstract: Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the function of hepatocytes isolated from steatotic donor livers. Human hepatocytes were isolated from 10 severely steatotic (>60%) donor livers rejected for transplantation. The left lateral segment of the donor liver was dissected into two equal size pieces and randomized to NAC or control. NAC (5 mM) was added to the first perfusion buffer of the standard collagenase digestion technique. Cells from tissues perfused with NAC had a significantly higher mean viability (81.1 ± 1.7% vs. 66.0 ± 4.7%; p = 0.003) and cell attachment (1.08 ± 0.26 vs. 0.67 ± 0.18 OD units; p = 0.012). Addition of NAC during isolation of human hepatocytes from steatotic donor liver tissue significantly improved the outcome of cell isolation. Further studies are needed to investigate the mechanism(s) of this effect. Incorporation of NAC in the hepatocyte isolation protocol could increase the availability of hepatocytes for transplantation.
authors.affiliation: Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK.
authors.forename: Filippos G
authors.initials: FG
authors.lastname: Sagias
authors.forename: Ragai R
authors.initials: RR
authors.lastname: Mitry
authors.forename: Robin D
authors.initials: RD
authors.lastname: Hughes
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Lehec
authors.forename: Ameet G
authors.initials: AG
authors.lastname: Patel
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rela
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Heaton
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002469:Cell Separation; D002470:Cell Survival; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D000111:Acetylcysteine