Leckel K, Blaheta R A, Markus B H
Klinik für Allgemein-, Visceral- und Transplantationschirurgie, Charité, Campus Virchow-Klinikum, Universitätsklinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Berlin.
Zentralbl Chir. 2003 Apr;128(4):283-90. doi: 10.1055/s-2003-38791.
Over the past few years, hepatocyte transplantation has been considered as an alternative method for orthotopic liver transplantation for the treatment of various liver diseases. Beside curative approach for genetic metabolic deficiencies (familial hypercholesterolemia, hemophilia, etc.), it could be a useful tool for bridging the waiting period until an appropriate donor organ is obtained. In preclinical animal studies, hepatocytes injected intraperitoneally, intraportally or into the spleen settle down in the diseased liver. This enables genetic modification to correct inborn metabolic deficiencies and improves survival in acute liver failure. In 1992, the first clinical transplantation of isolated hepatocytes in 10 patients was performed. In 1998, Fox and coworkers described the successful transplantation of allogeneic liver cells in a child with Crigler-Najjar syndrome. Accomplished studies of Strom et al. resp. Bilir et al. of the same year proved the effectiveness of liver cell transplantation for transient treatment of acute liver failure. Prerequisite of this cell-based therapeutic strategy is a sufficient amount of highly differentiated hepatocytes, hence, a well established in-vitro cell-culture technique is necessary to yield a reproducible number of proliferating hepatocytes and to preserve the physiological cell function. This review discusses the different experimental approaches regarding the cultivation of human hepatocytes and also the use of alternative cell sources (like animal hepatocytes, immortalized cells of human origin, progenitor cells from fetal human liver/liver stem cells) for hepatocyte transplantation.
在过去几年中，肝细胞移植已被视为原位肝移植治疗各种肝脏疾病的替代方法。除了治疗遗传性代谢缺陷（家族性高胆固醇血症、血友病等）的治愈方法外，它还可能是在获得合适的供体器官之前缩短等待期的有用工具。在临床前动物研究中，经腹腔、门静脉或脾脏注射的肝细胞会在患病肝脏中定居。这使得基因修饰能够纠正先天性代谢缺陷，并提高急性肝衰竭患者的生存率。1992年，首次对10名患者进行了分离肝细胞的临床移植。1998年，福克斯及其同事描述了对一名患有克里格勒-纳贾尔综合征的儿童成功进行同种异体肝细胞移植的情况。同年斯特罗姆等人及比利尔等人完成的研究证明了肝细胞移植对急性肝衰竭的临时治疗效果。这种基于细胞的治疗策略的前提是要有足够数量的高度分化的肝细胞，因此，需要一种成熟的体外细胞培养技术来产生可重复数量的增殖肝细胞，并保持细胞的生理功能。本文综述了关于人类肝细胞培养的不同实验方法，以及肝细胞移植中替代细胞来源（如动物肝细胞、人源永生化细胞、人胎儿肝脏祖细胞/肝干细胞）的使用情况。
