Evaluation of the performance of an hybrid artifical liver using three-dimensional culture of hepatocytes by hepatic failure small animals

肝衰竭小动物肝细胞三维培养杂交人工肝性能评价

• 批准号: 06453107
• 负责人: FUNATSU Kazumori
• 金额: $ 4.48万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06453107/
• 关键词: Primary hepatocytes; Three-dimensional culture; Hybrid artificial liver; Hepatic failure; Hepatic failure rat; Hepatic failure dog; Liver regeneration; Galactosamine; 初代ラット肝細胞; ポリウレタンフォーム(PUF); スフェロイド; 多細管型PUF充填層; ラット体外循環; アンモニア代謝

1. Last year, we could succeed in recovery of a light hepatic failure rat which induced by D-galactosamine, by our developed hybrid artificial liver support system using three dimensional culture of hepatocytes. This year, we tried to improve the artificial liver support system for recovery of a severer hepatic failure rat. Consequently, we could also succeed in the recovery of the severer hepatic failure rats (10% of the rats spontaneously died) by this support system (n=4). And a possibility of occuring of liver regeneration was found from the histochemical analysis of recovered rat liver.2. We tried to scale up the hybrid artificial liver support system for recovery of hepatic failure dogs. The volume of the artificial liver module for dog was about 300cm^3 which corresponded to about 100 times scaling up of the module (5cm^3) for rat. Dissolved oxygen concentration 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 was comparable with static culture of hepatocytes. And we could get an knowledge about optimum flow rate of medium related to reveal the maximum performance of the hybrid artificial liver module.

1. 去年，我们研制的肝细胞三维培养杂交人工肝支持系统成功恢复了d -半乳糖胺诱导的轻度肝衰竭大鼠。今年，我们试图改进人工肝支持系统，以恢复严重肝功能衰竭的大鼠。因此，我们也可以通过该支持系统成功地恢复严重肝功能衰竭大鼠（10%的大鼠自发死亡）（n=4）。对恢复的大鼠肝脏进行组织化学分析，发现肝再生的可能性。我们试图扩大混合人工肝支持系统的规模，以恢复肝衰竭的狗。狗人工肝模块的体积约为300cm^3，相当于大鼠人工肝模块（5cm^3）的约100倍。模块内介质的双向流动似乎避免了模块内溶解氧浓度梯度的发生。在该模块中固定的肝细胞的白蛋白分泌率表明，其性能与静止培养的肝细胞相当。从而获得相关介质的最佳流速，从而揭示混合式人工肝模块的最大性能。

项目成果

和田茂久: "肝不全ラットを用いた体外環境によるPUF/肝細胞スフェロイド充填層型人工肝臓の性能評価-最適装置条件の検討-(印刷中)" 人工臓器. 25. (1996)

Shigehisa Wada：“使用肝功能衰竭大鼠的体外环境对 PUF/肝细胞球体填充的人工肝脏进行性能评估 - 最佳装置条件检查 -（印刷中）”Artificial Organs 25。

N.Koide: "Hepatocyte spheroid:Differentiated features and potential utilization for the bioreactor of artificial liver support" Animal Cell Technology:Basic & Applied Aspects. 6. 99-101 (1994)

N.Koide：“肝细胞球体：人工肝支持生物反应器的差异化特征和潜在利用”动物细胞技术：基础

船津和守: "メディカルテクノロジーへの招待" 株式会社 培風館, 20 (1995)

船夏和森：《医疗技术的邀请》Baifukan Co., Ltd., 20 (1995)

Kohji Nakazawa: "Development of drug metabolism simulator for alternatives to animal experimentation using 3-dimensional culture of hepatocytes" Proc.of the 9th Ann.Meeting of Jpn.Soc.for Alternatives to animal Experiments. Vol.9. 114-115 (1995)

Kohji Nakazawa：“使用 3 维肝细胞培养物开发药物代谢模拟器，用于替代动物实验”Proc.of the 9th Ann.Meeting of Jpn.Soc.for Alternatives to Animal Experiments。

松下 琢: "肝不全ラット体外循環によるポリウレタンフォーム(PUF)/肝細胞スフェロイド充填層型人工肝臓の性能評価" 人工臓器. 24. 815-820 (1995)

Taku Matsushita：“使用体外循环对肝功能衰竭大鼠进行聚氨酯泡沫 (PUF)/肝细胞球填充人工肝脏的性能评估”Artificial Organs。