University of Amsterdam, Academic Medical Center, Department of Experimental Surgery (Surgical Laboratory; IWO 1A.1-117), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Expert Opin Biol Ther. 2012 Jul;12(7):905-21. doi: 10.1517/14712598.2012.685714. Epub 2012 May 31.
Bioartificial livers (BALs) are urgently needed to bridge severe liver failure patients to liver transplantation or liver regeneration. When based on primary hepatocytes, their efficacy has been shown in animal experiments and their safety was confirmed in clinical trials. However, a proliferative human cell source with therapeutic functionality is needed to secure availability and move BAL application forward.
This review compares the performance of BALs based on proliferative human biocomponents and primary hepatocytes. This review evaluates relevant studies identified by searching the MEDLINE database until July 2011 and some of our own unpublished data.
All the discussed hepatocyte-like biocomponents show deficiencies in their hepatic functionality compared with primary hepatocytes, particularly functions occurring late in liver development. Nonetheless, the HepaRG, HepG2-GS-CYP3A4, and mesenchymal stem cells show efficacy in a statistically well-powered animal model of acute liver failure, when applied in a BAL device. Various methods to gain higher functionality of BALs, including genetic modification, the usage of combinatory cell sources, and improvement of culture methods, have scarcely been applied, but may further pave the path for BAL application. Clinical implementation of a BAL based on a human proliferative biocomponent is still several years away.
生物人工肝脏（BAL）是为了弥补严重肝功能衰竭患者在等待肝移植或肝脏再生过程中的治疗空缺而研发的。以原代肝细胞为基础的生物人工肝脏已经在动物实验中显示出其疗效，并在临床试验中得到了安全性验证。但是，为了确保可用性，需要一种具有治疗功能的增殖性人类细胞源来推进生物人工肝脏的应用。
本文通过比较基于增殖性人类生物元件和原代肝细胞的生物人工肝脏的性能，来评估其临床应用的潜力。本文评估了通过搜索 MEDLINE 数据库直到 2011 年 7 月获得的相关研究，并使用了我们自己的一些未发表的数据。
与原代肝细胞相比，所有讨论的类肝细胞生物元件在其肝功能方面都存在缺陷，特别是在肝脏发育后期出现的功能。尽管如此，当应用于生物人工肝脏装置时，HepaRG、HepG2-GS-CYP3A4 和间充质干细胞在急性肝功能衰竭的动物模型中显示出统计学上的有效性。尚未广泛应用各种提高生物人工肝脏功能的方法，包括遗传修饰、使用组合细胞源和改进培养方法，但可能进一步为生物人工肝脏的应用铺平道路。基于人类增殖性生物元件的生物人工肝脏的临床应用仍需数年时间。
