title: Long-term maintenance of the drug transport activity in cryopreservation of microencapsulated rat hepatocytes.
abstract: Transplantation of isolated hepatocytes has been proposed to compensate for essential functions lacking in liver failure or for genetic defects that alter a specific liver metabolic pathway. Hepatocyte utilization for these purposes would be facilitated with a reliable, reproducible, and effective method of long-term hepatocyte storage. We have recently developed a simple new system for cryopreservation of hepatocytes that encapsulates alginate microspheres and maintains liver-specific function. The aim of this study was to elucidate the transport and drug-metabolizing enzyme activities of cryopreserved microencapsulated hepatocytes stored for a long time. Morphological examinations showed there is no apparent injury of the hepatocytes during cryopreservation processes. A drug-metabolizing enzyme (testosterone 6beta-hydroxylase, a specific probe for CYP3A2) and drug transport activities [salicylate, allopurinol, and prostaglandin E2 (PGE2), typical substrates of rOat2] in cryopreserved microencapsulated hepatocytes were maintained up to 120 days. Our results thus demonstrate for the first time that cryopreservation of primary rat hepatocytes by the encapsulation technique allows long-term retention of drug metabolism and drug transport activities.
authors: Second Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. t-koiz@med.showa-u.ac.jp
authors: Tomotake
authors: T
authors: Koizumi
authors: Takeshi
authors: T
authors: Aoki
authors: Yasuna
authors: Y
authors: Kobayashi
authors: Daisuke
authors: D
authors: Yasuda
authors: Yoshihiko
authors: Y
authors: Izumida
authors: Zhenghao
authors: Z
authors: Jin
authors: Nobukazu
authors: N
authors: Nishino
authors: Yoshinori
authors: Y
authors: Shimizu
authors: Hirohisa
authors: H
authors: Kato
authors: Noriyuki
authors: N
authors: Murai
authors: Takashi
authors: T
authors: Niiya
authors: Yuta
authors: Y
authors: Enami
authors: Keitaro
authors: K
authors: Mitamura
authors: Toshinori
authors: T
authors: Yamamoto
authors: Mitsuo
authors: M
authors: Kusano
mesh_terms: D000493:Allopurinol / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D017690:Cell Transplantation; D015925:Cryopreservation / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000637:transplantation; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D012459:Salicylates; D000493:Allopurinol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C022657:steroid hormone 6-beta-hydroxylase; D015232:Dinoprostone