A rapid and simple method for cryopreservation of human liver slices

R. de KANTER Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

P. OLINGA Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

I. HOF Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

M. de JAGER Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

W. A. VERWILLEGEN Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

M. J. H. SLOOFF Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

H. J. KOSTER Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

D. K. F. MEIJER Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

G. M. M. GROOTHUIS Drug Safety Department, Solvay Duphar B.V., P.O. Box 900, 1380 DA Weesp, The Netherlands OE Groningen Utrecht Institute for Drug Exploration (GUIDE), Department of Pharmacokinetics and Drug Delivery, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands Groningen Utrecht Institute for Drug Exploration (GUIDE), Division of Hepatobiliary Surgery and Liver Transplanta tion, Department of Surgery, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

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Abstract

1. Precision-cut liver slices represent a suitable and convenient in vitro preparation for studying metabolism and toxicity mechanisms of drugs and toxic chemicals.Particularly in the case of human liver slices, cryopreservation would enable more efficient utilization of this scarce and irregularly available tissue. 2. Liver slices from consecutive human livers were cryopreserved using a method previously developed for rat and monkey liver slices. This procedure involves incubation in 12% dimethyl sulphoxide for 30 min on ice and direct immersion into liquid nitrogen. 3. Functional integrity of cryopreserved human liver slices, as compared with that of fresh liver slices, was maintained at 66±8% (alanine aminotransferase activity retained in the slices), 78±7% (urea synthesis), 88±14% (testosterone hydroxylation), 84±7% (N-deethylation of lidocaine) and 88±10% (total O-deethylation of 7-ethoxycoumarin). The ratios of testosterone metabolites did not change on cryopreservation. 4. These results show that the cryopreserved human liver slices retained the measured drug metabolism activities. Therefore, this cryopreservation method is suitable for storing liver slices to be used for comparing drug metabolism patterns, at least qualitatively, between species.

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A rapid and simple method for cryopreservation of human liver slices

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