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STUDIES ON HYBRID ARTIFICIAL LIVERS IN POINTS OF THE TECHNOLOGY FOR ORGAN RECONSTRUCTION

混合型人工肝从器官重建技术角度的研究

基本信息

批准号：
04454307
负责人：
KASAI Shinichi
金额：
$ 1.15万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

Artificial liver and liver transplantation are the only way to replace the deteriorated functions of the damaged livers. However, complete replacement of the original liver functions is not yet possible for artificial livers today, and liver transplantation faces severe scarcity of donor livers.Recently, artificial livers such as hemodialysis, hemoperfusion, and plasmapheresis have been used clinically to treat patients with liver failure, but the survival rate has not so improved. One of the reasons for this poor survival rate appears to be a lack of metabolic support capacity for the damaged livers. In this study, the development of a hybrid artificial liver was studied in points of the technology for organ reconstruction. Combination of hepatocytes and artificial materials has been attempted to reconstruct the metabolic functions of liver.1) Natural substrata such as biomatrix of the liver and collagen, and synthetic substrata such as lactose-carrying polystirene were examined in primary culture of isolated hepatocytes, and these were useful for coating artificial materials.2) Artificial materials such as dextran microcarriers and cellulose multiporous microcarriers were investigated of their availability for immobilizing hepatocytes in a hybrid artificial liver. Hepatocytes immobilized to these microcarriers showed better NH3 and fructose metabolism.It was therefore suggested that these substrata and carriers were useful for the development of hybrid artificial livers.

人工肝和肝移植是替代受损肝脏功能退化的唯一途径。然而，目前人工肝脏还不可能完全替代原有的肝脏功能，肝移植也面临着供体肝脏严重短缺的问题。近年来，临床上已采用血液透析、血液灌流、血浆置换等人工肝脏治疗肝功能衰竭患者，但生存率并没有得到如此大的提高。生存率低的原因之一似乎是受损肝脏缺乏代谢支持能力。本研究从器官重建技术的角度对杂交人工肝的发展进行了研究。肝细胞与人工材料的结合已被尝试用于重建肝脏的代谢功能。1)在分离肝细胞原代培养中考察了天然基质（如肝脏生物基质和胶原蛋白）和人工基质（如携带乳糖的聚苯乙烯），这些基质可用于人工材料的包被。2)研究了葡聚糖微载体和纤维素多孔微载体等人工材料在杂交人工肝中固定肝细胞的可行性。固定在这些微载体上的肝细胞表现出更好的NH3和果糖代谢。因此，这些基质和载体对杂交人工肝的发展是有益的。