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| Content Provider | Springer Nature Link |
|---|---|
| Author | Brown, Lanika A. Arterburn, Linda M. Miller, Ana P. Cowger, Nancy L. Hartley, Sonya M. Andrews, Annette Silber, Paul M. Li, Albert P. |
| Copyright Year | 2003 |
| Abstract | Rat hepatocytes were cultured initially as spheroids on culture plates and then transferred into a rotating wall vessel (high-aspect ratio vessel [HARV]) for further culturing. Morphological evaluation based on electron microscopy showed that hepatocyte spheroids cultured for, 30 d in the HARV had a compact structure with tight cell-cell junctions, numerous smooth and rough endoplasmic reticulum, intact mitochondria, and bile canaliculi lined with microvilli. The viability and differentiated properties of the hepatocytes cultured in the HARV were further substantiated by the present of both phase I oxidation and phase II conjugation drug-metabolizing enzyme activities, as well as albumin synthesis. Homogenates preparated from freshly isolated hepatocytes and hepatocytes cultured in the HARV showed similar cytochrome P450 2B activities measured as pentoxyresorufin-O-dealkylase and testosterone 16β-hydroxylase. Further, intact hepatocytes cultured in the HARV were found to metabolize chlorozoxazone to 6-hydroxychlorzoxazone; dextromethorphan to dextrorphan, 3-methoxymorphinan, and 3-hydroxymorphinan; midazolam to 1-hydroxymidazolam and 4-hydroxymidazolam; and 7-hydroxycoumarin to its glucuronide and sulfate conjugates. In conclusion, we found that hepatocyte spheroids could be cultured in a HARV to retain cellular and physiological properties of the intact liver, including drug-metabolizing enzyme activities, plasma protein production, and long-term (1 mo) maintenance of viability and cellular function. |
| Starting Page | 13 |
| Ending Page | 20 |
| Page Count | 8 |
| File Format | |
| ISSN | 10712690 |
| Journal | In Vitro Cellular & Developmental Biology - Animal |
| Volume Number | 39 |
| Issue Number | 1-2 |
| e-ISSN | 1543706X |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2003-01-01 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | high-aspect ratio vessel cytochrome P450 pentoxyresorufin-O-dealkylase 7-hydroxycoumarin rotating wall vessel Cell Biology Developmental Biology Animal Genetics and Genomics Animal Biochemistry Animal Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Medicine |
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