RESEARCH ARTICLE
Differentiation of the human liver progenitor cell line (HepaRG) on a microfluidic-based biochip
Mi Jang,
Astrid Kleber,
Thomas Ruckelshausen,
Ralf Betzholz,
Andreas Manz,
Mi Jang
Department of system engineering, Saarland University, Saarbrücken, Germany
Microfluidics group, KIST Europe, Saarbrücken, Germany
Department of Neuroscience, Korea University College of Medicine, Seoul, Korea
Search for more papers by this authorAstrid Kleber
Rhineland Palantinate Centre of Excellence for climate Change Impacts, Trippstadt, Germany
Search for more papers by this authorThomas Ruckelshausen
Dynamic Biomaterial group, INM - Leibniz-Institut für Neue Materialien GmbH, Saarbrücken, Germany
Service and Support group, PicoQuant, Rudower Chaussee 29, Berlin, Germany
Search for more papers by this authorRalf Betzholz
School of Physics, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCorresponding Author
Andreas Manz
Department of system engineering, Saarland University, Saarbrücken, Germany
Microfluidics group, KIST Europe, Saarbrücken, Germany
Correspondence
Andreas Manz, KIST Europe, Campus E7, Saarbrücken 66123, Germany.
Email: [email protected]
Search for more papers by this authorMi Jang,
Astrid Kleber,
Thomas Ruckelshausen,
Ralf Betzholz,
Andreas Manz,
Mi Jang
Department of system engineering, Saarland University, Saarbrücken, Germany
Microfluidics group, KIST Europe, Saarbrücken, Germany
Department of Neuroscience, Korea University College of Medicine, Seoul, Korea
Search for more papers by this authorAstrid Kleber
Rhineland Palantinate Centre of Excellence for climate Change Impacts, Trippstadt, Germany
Search for more papers by this authorThomas Ruckelshausen
Dynamic Biomaterial group, INM - Leibniz-Institut für Neue Materialien GmbH, Saarbrücken, Germany
Service and Support group, PicoQuant, Rudower Chaussee 29, Berlin, Germany
Search for more papers by this authorRalf Betzholz
School of Physics, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorCorresponding Author
Andreas Manz
Department of system engineering, Saarland University, Saarbrücken, Germany
Microfluidics group, KIST Europe, Saarbrücken, Germany
Correspondence
Andreas Manz, KIST Europe, Campus E7, Saarbrücken 66123, Germany.
Email: [email protected]
Search for more papers by this authorAbstract
HepaRG is a bipotent stem cell line that can be differentiated towards hepatocyte-like and biliary-like cells. The entire cultivation process requires 1 month and relies on the addition of 2% dimethyl sulfoxide (DMSO) to the culture. Our motivation in this research is to differentiate HepaRG cells (progenitor cells and undifferentiated cells) towards hepatocyte-like cells by minimizing the cultivation time and without using DMSO treatment by instead using a microfluidic device combined with the following strategies: (a) comparison of extracellular matrices (matrigel and collagen I), (b) types of flow (one or both sides), and (c) effects of DMSO. Our results demonstrate that matrigel promotes the differentiation of progenitor cells towards hepatocytes and biliary-like cells. Moreover, the frequent formation of HepaRG cell clusters was observed by a supply of both sides of flow, and the cell viability and liver specific functions were influenced by DMSO. Finally, differentiated HepaRG progenitor cells cultured in a microfluidic device for 14 days without DMSO treatment yielded 70% of hepatocyte-like cells with a highly polarized organization that reacted to stimulation with IL-6 to produce C-reactive protein (CRP). This culture model has high potential for investigating cell differentiation and liver pathophysiology research.
CONFLICT OF INTEREST
The authors have declared that there is no conflict of interest.
Supporting Information
| Filename | Description |
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| term2802-sup-0001-st1.docxWord 2007 document , 12.4 KB |
Table S1. Albumin production and CYA1A induction fold change level in HepaRG 2D culture at 4 weeks of cultivation under fully differentiated condition supplemented by 2% of DMSO for 2 weeks. (The data represents the mean ± SD of 5 independent cultures.) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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