Effect of Preoperative Chemotherapy on the Isolation Outcome of Primary Human Hepatocytes

Abstract

Primary human hepatocytes isolated from surgically resected liver tissue are an essential resource for pharmaceutical and toxicological studies. Patients undergoing partial liver resections have often received preoperative chemotherapy. The aim of our study was to investigate whether preoperative chemotherapy has effects on the outcome of cell isolation or the metabolic function of cultured hepatocytes. Liver specimens from 48 patients were used for hepatocyte isolation. Out of these, 21 patients had prior chemotherapy, with fluoropyrimidine-based regimen in 14 patients. Viability and cell yield as parameter for the outcome of isolation, as well as transaminase-levels, urea or albumin secretion to the culture medium were not different between hepatocytes from pre-treated and un-treated donor. Furthermore, the transcription levels of CYP 1A2, CYP 2B6, and CYP 3A4 of cultured hepatocytes were not affected by prior chemotherapy of the tissue donors. In conclusion, hepatocytes from tissue donors that underwent fluoropyrimidine-based chemotherapy regimens prior to isolation seem to perform as well as hepatocytes without pre-operative chemotherapy exposure. Our results suggest that hepatocytes from patients who received combination chemotherapy prior to liver resection are an uncompromised resource for pharmacologic and toxicologic studies.