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Haque A, Gheibi P, Gao Y, et al. Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. Sci Rep. 2016;6:33980doi: 10.1038/srep33980.
Haque, A., Gheibi, P., Gao, Y., Foster, E., Son, K. J., You, J., Stybayeva, G., Patel, D., & Revzin, A. (2016). Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. Scientific reports, 633980. https://doi.org/10.1038/srep33980
Haque, Amranul, et al. "Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels." Scientific reports vol. 6 (2016): 33980. doi: https://doi.org/10.1038/srep33980
Haque A, Gheibi P, Gao Y, Foster E, Son KJ, You J, Stybayeva G, Patel D, Revzin A. Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels. Sci Rep. 2016 Sep 29;6:33980. doi: 10.1038/srep33980. PMID: 27681582; PMCID: PMC5041105.
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Sci Rep. 2016 Sep 29;6:33980. doi: 10.1038/srep33980.

Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels.

Scientific reports

Amranul Haque, Pantea Gheibi, Yandong Gao, Elena Foster, Kyung Jin Son, Jungmok You, Gulnaz Stybayeva, Dipali Patel, Alexander Revzin

Affiliations

  1. Department of Biomedical Engineering, University of California Davis, CA 95616, USA.
  2. Department of Plant and Environmental New Resources, Kyung Hee University, Youngin-si, Gyeonggi-do, South Korea.

PMID: 27681582 PMCID: PMC5041105 DOI: 10.1038/srep33980

Abstract

The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs-this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function.

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