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Development of a hybrid artifical liver using PUF/three dimensional culture of normal hepatocytes

利用 PUF/正常肝细胞三维培养开发混合型人工肝

基本信息

批准号：
04555225
负责人：
FUNATSU Kazumori
金额：
$ 10.37万
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：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

1. We designed a prototype of hybrid artificial liver module using optimum polyurethane foam (PUF) material for spheroid formation of hepatocyte in vitro. The module was type of packed-bed with PUF plates (1.5X40X40mm) which immobilized spheroids. In serum-free medium supplemented with 1mM NH_4Cl as a toxic substance, this module detoxified ammonia and synthesized urea from ammonia. The urea synthesis rate of hepatocyte in the module was slightly higher than that of hepatocyte in vivo and was maintained for about 3 weeks.2. We also developed Multi-Capillary PUF packed-bed for increasing a cell density and achieving an efficient mass transfer, in which a cylindrical PUF block with many capillaries for medium flow was packed. Consequently, a high cell density of 1X10^7cells/cm^3-PUF was achieved and hepatocyte/spheroids were formed in the module. The urea synthesis rate of the module was 10 times higher than that of prototype module.3. A volume of the hybrid artificial liver module containing 1/10 amount of human liver hepatocytes was estimated to be about 2 liter by using the Multi-Capillary PUF packed-bed. This volume seemed to be a medically applicable value.4. We developed an extracorporeal circulation system for acute hepatic failure rat to investigate the performance of the artificial liver module in ex vivo experiment. The ammonia concentration in blood increased by actute failure was gone down to normal level by the artificial liver for 3 hour circulation and the hepatic failure rat was recovered.

1.采用优化的聚氨酯泡沫（PUF）材料，设计了一种混合型人工肝模型。该模块是具有固定球状体的PUF板（1.5X40X40mm）的填充床类型。在添加1mM NH_4Cl的无血清培养基中，该组件可将氨解毒并合成尿素。该组件中肝细胞尿素合成速率略高于体内肝细胞，并能维持3周左右.我们还开发了多毛细管PUF填充床，以增加细胞密度并实现有效的传质，其中填充了具有许多用于介质流动的毛细管的圆柱形PUF块。因此，实现了1 × 10^7个细胞/cm^3-PUF的高细胞密度，并在模块中形成了肝细胞/球状体。该模块的尿素合成速率是原型模块的10倍.通过使用多毛细管PUF填充床，包含1/10量的人肝肝细胞的混合人工肝模块的体积估计为约2升。该体积似乎具有医学适用价值。4.为研究人工肝模块在体外实验中的性能，我们建立了急性肝功能衰竭大鼠体外循环系统。人工肝循环3h可使急性肝功能衰竭时血氨浓度下降至正常水平，使肝功能衰竭大鼠恢复正常。