title: Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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studies identified by searching the MEDLINE database until April 2014 were reviewed, supplemented with some of our own unpublished data.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Surgical Laboratory, and Tytgat Institute for Liver and Intestinal Research, Academic Medical Center , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands.
authors.forename: Martien
authors.initials: M
authors.lastname: van Wenum
authors.forename: Robert Afm
authors.initials: RA
authors.lastname: Chamuleau
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.forename: Adriaan
authors.initials: A
authors.lastname: Siliakus
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seppen
authors.forename: Ruurdtje
authors.initials: R
authors.lastname: Hoekstra
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation; D006801:Humans; D066298:In Vitro Techniques; D017093:Liver Failure / Q000628:therapy*; D019164:Liver, Artificial; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
keywords: HepaRG; bioartificial liver; drug induced liver injury; hepatitis; hepatocyte; hepatocyte like cell; iHEP; induced pluripotent stem cell; liver; stem cell