Microfluidic confinement enhances phenotype and function of hepatocyte spheroids.

American Journal of Physiology. Cell Physiology
Jong Hoon ChoiAlexander Revzin

Abstract

A number of cell culture approaches have been described for maintenance of primary hepatocytes. Forming hepatocytes into three-dimensional (3-D) spheroids is one well-accepted method for extending epithelial phenotype of these cells. Our laboratory has previously observed enhanced function of two-dimensional (2-D, monolayer) hepatocyte cultures in microfluidic devices due to increased production of several hepato-inductive growth factors, including hepatocyte growth factor (HGF). In the present study, we wanted to test a hypothesis that culturing hepatocyte spheroids (3-D) in microfluidic devices will also result in enhanced phenotype and function. To test this hypothesis, we fabricated devices with small and large volumes. Both types of devices included a microstructured floor containing arrays of pyramidal wells to promote assembly of hepatocytes into spheroids with individual diameters of ~100 µm. The hepatocyte spheroids were found to be more functional, as evidenced by higher level of albumin synthesis, bile acid production, and hepatic enzyme expression, in low-volume compared with large-volume devices. Importantly, high functionality of spheroid cultures correlated with elevated levels of HGF secretion. Although decay of...Continue Reading

References

Feb 1, 1992·The Journal of Cell Biology·J C DunnM L Yarmush
May 1, 1984·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B ClementA Guillouzo
Apr 1, 1996·Journal of Biochemistry·K Matsumoto, T Nakamura
Nov 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·F BerthiaumeM L Yarmush
Apr 1, 1997·Physiological Reviews·C S Lieber
Feb 4, 1999·Nature Medicine·T UekiJ Fujimoto
Nov 2, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S N BhatiaM Toner
May 12, 2004·Biotechnology and Bioengineering·Rachel GlicklisSmadar Cohen
Nov 21, 2007·Nature Biotechnology·Salman R Khetani, Sangeeta N Bhatia
Dec 15, 2007·Free Radical Biology & Medicine·Yongke Lu, Arthur I Cederbaum
Apr 21, 2009·Biomaterials·Caroline N JonesAlexander Revzin
May 26, 2009·Free Radical Biology & Medicine·Argelia Valdés-ArzateLuis Enrique Gómez-Quiroz
Sep 16, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sung Hwan KiBin Gao
Nov 8, 2011·Methods in Molecular Biology·Daniel KnobelochAndreas K Nussler
Oct 30, 2012·Clinics in Liver Disease·Arthur I Cederbaum
Aug 6, 2014·Nature Biotechnology·Sangeeta N Bhatia, Donald E Ingber
Jun 25, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Dipali PatelAlexander Revzin
Jul 15, 2015·Biotechnology and Bioengineering·Ljupcho ProdanovOsman Berk Usta
Mar 1, 2016·Gastroenterology·Suthat LiangpunsakulGeoffrey W McCaughan
Jun 24, 2017·American Journal of Physiology. Cell Physiology·Yaming LiuVijay H Shah
Jul 20, 2018·BMJ : British Medical Journal·Elliot B Tapper, Neehar D Parikh
Sep 30, 2018·Journal of Hepatology·Sumeet K AsraniPatrick S Kamath

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Citations

Oct 2, 2020·Biological Reviews of the Cambridge Philosophical Society·Ogechi OgokeNatesh Parashurama
Jun 18, 2021·Seminars in Liver Disease·David A Kukla, Salman R Khetani

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Methods Mentioned

BETA
Assay
scanning electron microscopy
ELISA
confocal microscopy

Software Mentioned

GraphPad Prism
COMSOL

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