title: Human liver quality is a dominant factor in the outcome of in vitro studies.
abstract: Donated human liver in the form of precision-cut tissue slices or isolated hepatocytes, is increasingly being used to predict metabolism and toxicity of xenobiotics in man. These tissue slices or hepatocytes can also be cold-preserved and cryopreserved to prolong their use for biological experiments. The viability of human liver could substantially affect the outcome of such experimentation. The goal of this investigation was to assess the viability of donated human livers, in the form of tissue slices, as they were received and to determine how varying degrees of liver quality affect experimental outcomes. Over one hundred human livers were categorized according to initial viability, as assessed by ATP content, K+ retention, protein synthesis, and LDH leakage. Each liver was placed in a low-, a medium-, or a high-quality group. The results showed that 76% of transplant-grade tissue (procured for transplantation) fell into the high-viability classification while the majority of research-grade tissue (not procured for transplantation) fell into the lowest viability classification. It was also found that only tissue slices prepared from highly viable human liver could be cold-preserved and cryopreserved. Dichlorobenzene metabolism was also greater in slices from highly viable human livers as compared to less viable livers. This study showed that human liver tissue acquired for medical research substantially varies in its viability and that these differences will affect the experimental data obtained.
authors.affiliation: Vitro, Inc., Tucson, Arizona 85747, USA. robyn@vitron.com
authors.forename: R L
authors.initials: RL
authors.lastname: Fisher
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
authors.forename: K
authors.initials: K
authors.lastname: Brendel
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D002722:Chlorobenzenes / Q000493:pharmacokinetics; D015925:Cryopreservation / Q000592:standards; D003584:Cytological Techniques / Q000592:standards*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000378:metabolism; D014176:Protein Biosynthesis; D014019:Tissue Donors
chemical_list: D002722:Chlorobenzenes; D007306:Insecticides; C004726:2-dichlorobenzene; C042146:1,3-dichlorobenzene; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D011188:Potassium