Long-Term Maintenance of the Drug Transport Activity in Cryopreservation of Microencapsulated Rat Hepatocytes
| Autor: | Tomotake Koizumi, Takeshi Aoki, Yasuna Kobayashi, Daisuke Yasuda, Yoshihiko Izumida, Zhenghao Jin, Nobukazu Nishino, Yoshinori Shimizu, Hirohisa Kato, Noriyuki Murai, Takashi Niiya, Yuta Enami, Keitaro Mitamura, Toshinori Yamamoto, Mitsuo Kusano |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Cell Transplantation, Vol 16 (2007) |
| Druh dokumentu: | article |
| ISSN: | 0963-6897 1555-3892 00000000 |
| DOI: | 10.3727/000000007783464489 |
| Popis: | 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 6β-hydroxylase, a specific probe for CYP3A2) and drug transport activities [salicylate, allopurinol, and prostaglandin E 2 (PGE 2 ), 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. |
| Databáze: | Directory of Open Access Journals |
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