EFFECT OF HUMAN LIVER SOURCE ON THE FUNCTIONALITY OF ISOLATED HEPATOCYTES AND LIVER SLICES

In vitro experiments using human liver tissue to study drug metabolism and transport are usually performed and interpreted without real cons ideration of the differences in procurement of the tissue, if it is ob tained from different sources. Therefore, in this study the functional ity of isolated hepatocytes and liver slices prepared either from heal thy human liver tissue obtained from patients undergoing partial hepat ectomy [livers from partial hepatectomy (PH-livers)] or from donor tis sue remaining after reduced-size or split-liver transplantation [liver s from transplantation (Tx-livers)] was compared. From each liver samp le, both liver slices and hepatocytes were prepared and compared with respect to viability and drug disposition. The viability of hepatocyte s was assessed by trypan blue exclusion, ATP content, and energy charg e and that of liver slices by potassium retention. In both preparation s phase I metabolism was studied using lidocaine and testosterone as s ubstrates, whereas phase I and II metabolism was assessed with 7-ethox ycoumarin. The membrane transport capability of the hepatocytes was in vestigated by measuring the uptake of taurocholic acid. The hepatocyte s from PH-livers and Tx-livers showed similar viabilities and function al capacities. Metabolism in cells and slices from Tx-livers was found to be quantitatively comparable. However, liver slices from PH-livers showed a significantly lower metabolic capacity, compared with cells from the same tissue. This may indicate that only some of the hepatocy tes in the liver slices from PH-livers participate in the metabolism o f the compounds studied and that a selection of healthy cells takes pl ace during isolation of the hepatocytes. Our results imply that hepato cytes isolated from Tx-livers and PH-livers can be used in the same st udy without consideration of the procurement of the tissue. However, t he procurement of the tissue may significantly influence the functions of liver slices; the liver slices prepared from PH-livers showed sign ificantly lower metabolic function, compared with slices prepared from Tx-livers.