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

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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Article number33980
JournalScientific reports
Volume6
DOIs
StatePublished - Sep 29 2016

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Cell biology is different in small volumes: Endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels'. Together they form a unique fingerprint.

Cite this