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Development of high performance hybrid artificial liver and its evaluation in preclinical test

高性能混合型人工肝的研制及其临床前评价

基本信息

批准号：
08555206
负责人：
FUNATSU Kazumori
金额：
$ 9.02万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08555206/
关键词：
Hybrid artificial liver Plasma of hepatic failure patient Hepatocyte spheroid Polyurethane foam Multi-capillary PUF packed-bed Extracorporeal circulation lschemic liver failure dog lschemic liver failure pig ブタ肝細胞スフェロイド多細管PUF充填層温虚血肝不

项目摘要

1.We developed a perfusion culture system of porcine hepatocyte spheroids (module volume ; 18.8cm^3, cell weight ; 2g, total plasma volume ; 140ml), and evaluated the functions of the spheroids in plasma of hepatic failure patient. Porcine hepatocyte spheroids mainatained ammonia decreasing activity in human plasma at least 3 days of culture.2.For a validation of the performance of our artificial liver using large animals, we made hybrid artificial liver module (multi-capillary polyurethane foam (PUF) packed-bed, vulume ; 380 cm ^3) containing 30 g of dog hepatocyte which corresponded about 10% of a dog liver weight. When the module was applied to ischemic liver failure dogs (body weight ; 15 kg), blood glucose concentration was maintained, increase of blood ammonia concentration was suppressed and so on by the artificial liver treatment. These performances were comparable or slightly superior than those of Demetriou's artificial liver which was already used clinically as a bridge use for liver transplantation.3.As preclinical step, we developed an artificial liver module using porcine hepatocyte spheroids (volume ; 380 cm^3*2) containing 64 g of cells, and applied to ischemic liver failure pigs (body weight ; 25 kg). Consequently, we could succeed suppression of the increase of blood ammonia concentration and extension of survival time.These results suggest that our hybrid artificial liver system is a promising equipment for recovery from hepatic failure condition in human medical care.

1.建立了猪肝细胞球体(模块体积18.8 cm~2，细胞重量；总血浆体积2g，140ml)的灌流培养体系，并对肝功能衰竭患者血浆中球体的功能进行了评价。2.为了验证我们人工肝的性能，我们用大型动物制作了混合型人工肝模块(多毛细管聚氨酯泡沫(PUF)填充床；380 cm^3)，其中包含30 g狗肝细胞，相当于狗肝脏重量的10%。将该模块应用于15 kg体重的缺血性肝衰竭犬，人工肝治疗可维持血糖浓度，抑制血氨浓度升高等。这些性能与Demetriou人工肝相当或略高于已被临床用作肝移植桥梁的人工肝。3.作为临床前步骤，我们开发了一种人工肝模块，使用含有g细胞的猪肝细胞球形(体积为380 cm^3*2)，并应用于缺血性肝衰竭猪(体重25 kg)。因此，我们成功地抑制了血氨浓度的升高，延长了生存时间。这些结果表明，我们的混合型人工肝系统是一种在人类医疗保健中有前景的肝功能衰竭恢复设备。