[Network for the collection and distribution of Japanese liver tissues resected surgically for drug development and research use].
We focused on the establishment of a trial procedure for the collection and distribution of Japanese liver tissues obtained from waste surgical resections for drug development and research use. The following procedures were prepared for this project: the pretreatment of liver tissues before storage, their storage at 4 degrees C, the transport of liver samples, the setting up of a communication network among the participating hospitals and laboratories and the approval of each ethics committee. Thirteen liver samples (1.6-7.6 g) obtained from patients whose livers were excised due to cirrhosis, hepatocellular carcinoma, cholangiocarcinoma, or metastasis from colorectal carcinoma and were donated for research. Informed consent was obtained from every patient. Freshly isolated human hepatocytes were prepared from nine liver samples (viability 34.3-86.1%). Four samples were unsuitable to prepare hepatocytes. The profile of testosterone metabolism as 6beta-, 2beta-, 16beta-, 16alpha- and 2alpha-hydroxytestosterone and androstenedione in freshly isolated hepatocytes was shown to be specific for human liver. The 6beta-hydroxylation activity catalyzed by CYP3A4/5 indicated a high level of metabolism (139-996 pmol/min/million cells). Levels of 7-ethoxycoumarin O-deethylation and glucronidation activities were sufficient for analysis in freshly isolated human hepatocytes. We conclude that liver tissues from waste surgical resections supplied from a participating hospital can constitute a valuable source of freshly isolated human hepatocytes for drug development and safety evaluation.
Department of Surgery II, Dokkyo University School of Medicine. sunouchi@nihs.go.jp
Momoko
M
Sunouchi
Kazue
K
Sakemi
Kei-ichi
K
Kubota
Junji
J
Kita
Yuichiro
Y
Kamikawa
Kohsuke
K
Uchida
Shin-ichi
S
Miura
Eiji
E
Shigehara
Hiroyuki
H
Fujioka
Yasuo
Y
Ohno
D000368:Aged; D002469:Cell Separation; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D015195:Drug Design; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007564:Japan; D008099:Liver; D008297:Male; D008506:Medical Waste; D008875:Middle Aged; D012106:Research; D013048:Specimen Handling; D013739:Testosterone / Q000378:metabolism
D008506:Medical Waste; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; C473667:cytochrome P-450 CYP3A45