Effect of low temperature preservation and cell density on metabolic function in a bioartificial liver |
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Authors: | Yueng Guen Park Takehiko Tosha Satoshi Fujita Boru Zhu Hiroo Iwata Hwa-Won Ryu |
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Affiliation: | (1) Institute for Frontier Medical Science, Kyoto University, 606 8507 Kyoto, Japan;(2) Faculty of Applied Chemical Engineering, Chonnam National University, 500-757 Gwangju, Korea;(3) Institute of Bioindustrial Technology, Chonnam National University, 500-757 Gwangju, Korea |
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Abstract: | Difficulties associated with bioartificial liver (BAL) preservation limit not only the commercialization of BAL, but also its clinical trials. In this study, the possibility of cold preservation of BAL cartridges containing porcine hepatocytes was examined at 4 °C. In anin vitro perfusion culture system, BAL cartridges maintained cytochrome P450 metabolic function for at least 50 days. However, all BAL cartridges completely lost their ammonia eliminating ability when stored at 4 °C. We also studied the effect of cell density on the maintenance of BAL liver function in a highly differentiated and healthy state. As expected, BALs containing a larger number of hepatocytes demonstrated higher metabolic functions. When metabolic functions were compared per gram of hepatocytes, no large differences were observed between devices containing different densities of hepatocytes. Decreased cell density did not successfully prolong BAL function. The viability and function of isolated hepatocytes highly depend on the culture conditions, such as cell density, substrata, culture media, and additives to the culture media. Perfusion culture of BAL cartridges at 4°C gave a promosing result with respect to the maintenance of P450 activity. However, as indicated by the rapid loss of ammonia metabolic activity, many factors still remain to be optimized for preservation of BAL keeping high metabolic functions for a longer time. |
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Keywords: | cold preservation bioartificial liver lidocaine ammonia cell density |
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