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Proliferative human cell sources applied as biocomponent in bioartificial livers: a review
Geert A A Nibourg1, Robert A F M Chamuleau, Thomas M van Gulik
1University of Amsterdam, Academic Medical Center, Department of Experimental Surgery (Surgical Laboratory; IWO 1A.1-117), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Expert Opinion on Biological Therapy
|June 2, 2012
Summary
Bioartificial livers (BALs) require proliferative human cells for severe liver failure. While current cell sources show promise in animal models, clinical use of BALs faces challenges and is years away.
Area of Science:
- Hepatology
- Regenerative Medicine
- Biotechnology
Background:
- Bioartificial livers (BALs) are crucial for bridging patients with severe liver failure to transplantation or regeneration.
- Primary hepatocytes have demonstrated efficacy and safety in BALs, but their limited availability necessitates alternative cell sources.
- A proliferative human cell source with therapeutic functionality is essential for advancing BAL applications.
Purpose of the Study:
- To compare the performance of BALs utilizing proliferative human biocomponents versus primary hepatocytes.
- To review existing literature and unpublished data on BALs up to July 2011.
Main Methods:
- Systematic literature search of the MEDLINE database.
- Inclusion of unpublished data from the authors' research.
- Comparative analysis of BAL performance based on different cell sources.
Main Results:
- Hepatocyte-like biocomponents exhibit functional deficiencies compared to primary hepatocytes, especially in late-stage liver development functions.
- HepaRG, HepG2-GS-CYP3A4, and mesenchymal stem cells demonstrated efficacy in a robust animal model of acute liver failure within a BAL device.
- Methods like genetic modification and improved culture techniques remain underexplored for enhancing BAL functionality.
Conclusions:
- While promising, proliferative human cell sources currently show functional limitations compared to primary hepatocytes.
- Specific cell lines and stem cells show potential in animal models for acute liver failure BALs.
- Further research into enhancing cell functionality and culture methods is needed for clinical translation, which remains several years away.
