生物人工肝支持系统中细胞材料的选择

Selection of cell materials in bioartificial liver support system

学术背景:以培养肝细胞为基础的生物人工肝支持系统是治疗肝衰竭和重型肝炎的重要方法之一,装有细胞材料的生物反应器则是其重要组成部分,而理想的生物人工肝细胞材料应具备成熟肝细胞的所有功能。目的:了解近年来国内外有关生物人工肝细胞材料的研究情况和最新进展。检索策略:主要检索1994-01/2007-06美国国立图书馆网站(PUBMED)、国内全文网站康健西文生物医学期刊文献数据库和中文CHKD网站有关生物人工肝细胞材料的文献,主要为英文检索,辅以中文。关键词为人工肝(liver,artificial)和/或肝细胞(Hepatocytes),干细胞(stemcell),肝细胞系(Livercellline)和永生化肝细胞(immortalization hepatocytes)。检索到685篇文献,不采用未发表的文章。经初步筛查,排除研究目的不同及内容重复的文献,详细阅读27篇。文献评价:所选文献主要来源于Hepatology,Journal of Artificial Organs,Gastroen terology,Annals of Surgery,Tissue Engineering,Journalof Hepatology,Biomaterials等著名杂志,主要为论著。资料综合:目前国内外用于生物人工肝的细胞主要有以下几种:①成人肝实质细胞:主要体现在安全性好,细胞生物学功能相同,最大障碍是来源匮乏,活力难以长时间维持。②猪肝细胞:是生物人工肝支持装置中应用最多的细胞材料,目前已进入Ⅱ/Ⅲ期临床研究,但在使用过程中需密切注意免疫反应和内源性反转录病毒感染的问题。③肝细胞株:是重要的生物人工肝细胞材料之一,来源容易。依靠其获得方法不同,可分为肝肿瘤源性、经传代建立以及病毒转染后的细胞株。④肝干细胞:是非常有潜力的细胞材料,可分为肝源性肝干细胞和非肝源性肝干细胞。结论:目前应用于生物人工肝临床研究的肝细胞主要有猪肝细胞和肝肿瘤细胞株,各有优缺点,永生化人肝细胞、肝干细胞等能否应用于临床,仍需深入探究。

BACKGROUND： Bioartificial liver support system （BALSS） based on cultured hepatocytes is an important measure to treat patients suffered liver failure or severe hepatitis. Bioreactor with cell material is an important part of it. Ideal cells for BALSS should have all the functions of normal human hepatocytes. OBJECTIVE： To summarize the research and present development of matedal of bioartificial liver. RETRIEVE STRATEGY：This article was retrieved mainly in English on the three network stations （www. Pubmed.com; www. kjmed.com.cn; www.CHKD.com.cn） with the key words of ＂artificial liver, hepatocytes, stem cell, liver cell line, immortalization hepatocytes＂. More than 685 pieces of articles were found. Non-published articles were excluded. By primary screening, most of them with different aims or repetitive content were rejected, and 27 pieces references were detailed studied. LITERATURE EVALUATION：Main sources of selected articles were these famous magazines, Hepatology, Journal of Artificial Organs, Gastroenterology, Annals of Surgery, Tissue Engineering, Journal of Hepatology and Biomaterials. Most articles were treatise. DATA SYNTHESIS： Now the cells used in BALSS mainly include ①human hepatocytes： Its biological functions are same to the patient＇s hepatocytes, and reliability is good. But the biggest problems are the short of source and cell viabilities are low and difficult maintained. ②Porcine hepatocytes are used at most in BALSS, some Ⅱ/Ⅲ phase clinical trial with porcine hepatocytes have been done, at the same time, the problem about immune reaction and porcine endogenous retroviral infection should be considered. ③Liver cell line is one of important cell material in bioartificial liver with its easy source. It can be divided into tumor derived cell line, passage established and viral transfection types according obtaining method. ④Liver stem cells are potential cell matedal of bioartificial liver and can be divided into liver derived stem cells and non-liver derived stem cells. CONCLUSION：Now the cell materials used in BALSS mainly have porcine and liver tumor cell line, whether liver stem cell and immortalization hepatocytes can be used in clinical must be further studied.