van Wenum Martien, Chamuleau Robert Afm, van Gulik Thomas M, Siliakus Adriaan, Seppen Jurgen, Hoekstra Ruurdtje
Surgical Laboratory, and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands.
Expert Opin Biol Ther. 2014 Dec;14(12):1745-60. doi: 10.1517/14712598.2014.950651. Epub 2014 Nov 4.
Bioartificial livers (BALs) were originally developed to treat patients suffering from severe liver failure and relied on primary hepatocytes or on hepatoblastoma-derived cell lines. Currently, new in vitro BAL applications are emerging, including drug toxicity testing, disease modeling and basic clinical research, and in recent years, advances in the field of stem cell biology have resulted in potential alternative cell sources.
This review identifies the demands of clinical and in vitro BAL applications to their biocomponent and summarizes the functionality and developmental state of BAL technology and cell types currently available. Relevant studies identified by searching the MEDLINE database until April 2014 were reviewed, supplemented with some of our own unpublished data.
BALs have the potential to meet demands currently left unmet in both clinical and in vitro applications. All the reviewed biocomponents show limitations towards one or more BAL applications. However, the generation of stem cell-derived hepatocyte-like cells is progressing rapidly, so the criteria for patient-specific drug toxicity screening and disease modeling are probably met in the near future. HepaRG cells are the most promising biocomponent for clinical BAL application, based on their proliferative and differentiation capacity.
生物人工肝（BAL）最初是为治疗严重肝功能衰竭患者而开发的，依赖于原代肝细胞或肝母细胞瘤衍生的细胞系。目前，新的体外BAL应用正在兴起，包括药物毒性测试、疾病建模和基础临床研究，近年来，干细胞生物学领域的进展带来了潜在的替代细胞来源。
本综述确定了临床和体外BAL应用对其生物成分的需求，并总结了BAL技术和目前可用细胞类型的功能及发展状态。对截至2014年4月通过检索MEDLINE数据库确定的相关研究进行了综述，并补充了我们自己的一些未发表数据。
BAL有潜力满足目前临床和体外应用中尚未满足的需求。所有综述的生物成分在一种或多种BAL应用方面都显示出局限性。然而，干细胞衍生的肝细胞样细胞的生成正在迅速进展，因此在不久的将来可能满足患者特异性药物毒性筛查和疾病建模的标准。基于其增殖和分化能力，HepaRG细胞是临床BAL应用中最有前景的生物成分。
