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Development of an hybrid artificial liver for human medical use equipped with the newest regulation system for control of culture environment of hepatocytes

开发配备最新肝细胞培养环境控制系统的医用混合人工肝

基本信息

批准号：
06555248
负责人：
FUNATSU Kazumori
金额：
$ 7.3万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

1. We developed a prototype module (multi-capillary PUF packed-bed) of hybrid artificial liver for recovery of hepatic failure dogs, which was required for an evaluation of the performance of this module using PUF/spheroid packed-bed for human medical use. Last year, we could succeed in recovery of a hepatic failure rat treated by 5cm^3 of module containing about 5*10^7 cells which corresponded to about 10% of liver cells. In the case of dog, we designed about 300cm^3 of module containing 3*10^9 cells (30g of cells) which corresponded to about 10% of dog liver cells. The diameter and the pitch of a capillary were 2mm and 4mm, respectively.2. Opimum flow rate of medium/plasma related to reveal the maximum performance of the hybrid artificial liver module was calculated to be 400 ml/min from the results of small scale experiment using rat. Dissolved oxygen concentration (DO) gradient occurred in the module seemed to be avoided by bi-directional flow of medium inside of the module. The performance which indicated by albumin secretion rate of hepatocytes immobilized in the module under pH ; 7.2 and DO ; 6.5 of controlled culture condition, was comparable with static culture of hepatocytes. These results indicated that the scale up of module was successful.3. We applied this artificial liver module to acute ischemic liver failure dogs for evaluation of practicality of the module for human medical care, and investigated the change of some biochemical components in blood as index of liver function. Consequently, we could succeed in the maintenance blood glucose level and ketone body ratio, and suppress the increase of blood ammonia and bilirubin levels. These results suggest that the artificial liver module is a promising equipment for recovery of hepatic failure condition in medical use.

1.我们开发了一个原型模块（多毛细管PUF填充床）的混合人工肝衰竭的狗，这是需要使用PUF/球体填充床的性能评价，该模块用于人类医疗用途。去年，我们成功地恢复了一只肝衰竭大鼠，该大鼠接受了5cm^3含有约5*10^7个细胞（相当于约10%的肝细胞）的模块治疗。在狗的情况下，我们设计了约300 cm^3的模块，包含3*10^9个细胞（30 g细胞），相当于约10%的狗肝细胞。毛细管直径为2 mm，螺距为4 mm.根据使用大鼠的小规模实验的结果，计算出与显示混合人工肝模块的最大性能相关的培养基/血浆的最佳流速为400 ml/min。组件内介质的双向流动避免了组件内溶解氧浓度（DO）梯度的产生。在pH7.2和DO 6.5的控制培养条件下，固定在模块中的肝细胞的白蛋白分泌速率指示的性能与肝细胞的静态培养相当。这些结果表明，模块的放大是成功的.我们将此人工肝模块应用于急性缺血性肝功能衰竭犬，以评估该模块在人类医疗保健中的实用性，并研究血液中某些生化成分作为肝功能指标的变化。因此，我们可以成功地维持血糖水平和酮体比率，并抑制血氨和胆红素水平的升高。这些结果表明，人工肝模块是一种很有前途的设备，用于肝功能衰竭的恢复在医疗用途。