TY - JOUR
T1 - Bioartificial livers in vitro and in vivo
T2 - Tailoring biocomponents to the expanding variety of applications
AU - Van Wenum, Martien
AU - Chamuleau, Robert Afm
AU - Van Gulik, Thomas M.
AU - Siliakus, Adriaan
AU - Seppen, Jurgen
AU - Hoekstra, Ruurdtje
N1 - Funding Information: The research leading to these results has received funding from the European Community’s Seventh Framework Programme FP7/2007-2013 under grant agreement n 304914. R Hoekstra, is a part time employee of the university spin-off company Hep-Art Medical Devices B.V, that holds the exclusive licence to the AMC-Bioartificial liver. Robert Chamuleau, is Chief Scientific Officer of Hep-Art Medical Devices B.V. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: © 2014 Informa UK, Ltd. All rights reserved. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Introduction: 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. Areas covered: 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studies identified by searching the MEDLINE database until April 2014 were reviewed, supplemented with some of our own unpublished data. Expert opinion: 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.
AB - Introduction: 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. Areas covered: 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. Expert opinion: 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.
KW - Bioartificial liver
KW - Drug induced liver injury
KW - HepaRG
KW - Hepatitis
KW - Hepatocyte
KW - Hepatocyte like cell
KW - Induced pluripotent stem cell
KW - Liver
KW - Stem cell
KW - iHEP
UR - http://www.scopus.com/inward/record.url?scp=84910096805&partnerID=8YFLogxK
U2 - https://doi.org/10.1517/14712598.2014.950651
DO - https://doi.org/10.1517/14712598.2014.950651
M3 - Review article
C2 - 25366164
SN - 1471-2598
VL - 14
SP - 1745
EP - 1760
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 12
ER -