Project/Area Number |
07458238
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
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Research Institution | The Jikei University School of Medicine |
Principal Investigator |
NAGAMORI Seishi The Jikei University School of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60119831)
|
Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Satoru Central Laboratories for Key Technology, Kirin Brewery Co., LTD.Chief Investigat, 基礎技術研究所, 主任研究員
NIIYA Minoru The Jikei University School of Medicine, Faculty of Medicine, Investigator, 医学部, 助手 (20198419)
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Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
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Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥5,100,000 (Direct Cost: ¥5,100,000)
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Keywords | Liver Support System / Radial Flow / Bioreactor / hepatic failure / JHH / nafamostat mesilate / Three dimensional culture / electron-microscopy / 人工肝臓 / ヒト肝細胞 / ラジアルフロー型バイオリアクター / アルブミン / アルファ・フェト・プロテイン / アンモニア / 体外循環 |
Research Abstract |
We have designed a large scale, high density culture of human hepatoma cells using as an artificial liver. An artificial liver support system (ALSS) could be significant as a therapy for acute hepatic failure and an intermediate step prior to liver transportation, however high cell density and continuous culture of human cell line is difficult. Since a radial flow bioreactor makes medium flow radially across the bed, a supply of nutrients and oxygen with low shear stress is possible. Using this bioreactor, high cell density cultivation (1.5x10^8 cells/ml-matrix, total 3x10^<10> cells) can be maintained for more than 70days. In this system, a microcomputer automatically controls the culture conditions to appropriately. Capacity of the bed in this bioreactor in 50-40ml. In this study, human hepatoma cell lines (JHH series) were used. JHH metabolized ammonia and products urea, thereby addressing the problem of hepatic coma induced by increased ammonia concentrations during hepatic failure. JHH consumed glucose 30g/day and released albumin at 13.9g/day in this system, a value similar to that of normal human liver. Using exracorporal ALSS and this bioreactor, we examined metabolism of nafamostat mesilate and production of prostaglandins. Three dimensional culture was observed by scanning and transmission electron-microscopy in this ALSS.
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