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Development of Hybrid Artificial Liver for Clinical Treatment of Fulminant Hepatic Failure Patient

混合型人工肝的开发用于临床治疗暴发性肝衰竭患者

基本信息

批准号：
10305062
负责人：
FUNATSU Kazumori
金额：
$ 21.95万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

1. Establishment of mass isolation method of porcine hepatocytesWe established two step collagenase treatment method for mass isolation of porcine hepatocytes. This method consists of liver perfusion and cell process using collagenase solution. More than 380g porcine hepatocytes (viability : more than 85%) were isolated within 3 hours from two pig livers (570g) by this method.2. Development of a hybrid artificial liver for children treatmentWe developed a multi-capillary polyurethane foam (PUF) packed-bed module (diameter : 7.7cm, height : 20cm, volume : 1000cmィイD13ィエD1) with 100g of porcine hepatocytes for clinical application. Porcine hepatocytes in the module formed spheroids within 24 hours of culture and maintained liver specific functions at least 10days of culture. We also developed extracorporeal circulation system for an artificial liver treatment, with control of DO, pH and temperature in plasma, and refinement of circulation loop for sufficient mass transfer.3. Preclinical tests of a hybrid artificial liver using failure pigsAs a preclinical test, we developed as artificial liver module with 200g of porcine hepatocytes, and applied to warm ischemic liver failure pigs of 25kg. Consequently, we could successfully indicate the care effect by the artificial liver in suppression of increase of blood ammonia, maintenance of blood glucose, extension of survival time and so on.4. Study of modulation of immunologic reaction between human serum and porcine hepatocytesWhen the porcine hepatocytes were cultured in human serum, immunologic reaction of human C3 against porcine hepatocytes occurred positively. We found that damage of porcine hepatocytes by human C3 could be decreased by the addition of nafamostat mesliate.These results suggest that our device will become a promising method for clinical treatment. At present, the device have been applied to the Ethics Committee of Kyushu University for clinical application.

1.猪肝细胞质量分离方法的建立建立了猪肝细胞质量分离的两步胶原酶处理法。该方法包括肝脏灌流和使用胶原酶溶液的细胞处理。结果：1.用此法可在3小时内从2个猪肝(570g)中分离出380g以上的猪肝细胞(存活率大于85%)。一种用于儿童治疗的混合型人工肝的研制我们用100g猪肝细胞研制了一种多毛细管聚氨酯泡沫填充床模块(直径：7.7 cm，高：20 cm，体积：1000 cmィイD13ィエD1)，用于临床应用。该模块中的猪肝细胞在培养24小时内形成球形，并在培养至少10天后保持肝脏特异性功能。我们还开发了用于人工肝治疗的体外循环系统，通过控制血浆中的DO、pH和温度，并改进了循环回路，以实现足够的质量传递。作为临床前试验，我们研制了含有200g猪肝细胞的人工肝模块，并将其应用于25公斤重的热缺血肝衰竭猪。说明人工肝在抑制血氨升高、维持血糖、延长生存时间等方面具有良好的护理效果。人血清与猪肝细胞免疫反应调节的研究猪肝细胞在人血清中培养时，人C3对猪肝细胞的免疫反应呈阳性。我们发现加入奈法莫他汀可以减轻人C3对猪肝细胞的损伤。这些结果表明，我们的装置将成为一种有希望的临床治疗方法。目前，该装置已在九州大学伦理委员会进行临床应用。