A New Liver Support System Using a Radial Flow Bioreactor

点击翻译按钮获取中文摘要

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.