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Digestive Diseases and Sciences

, Volume 57, Issue 5, pp 1152–1162 | Cite as

A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells

  • Hiroyuki EdaEmail author
  • Katherine M. Kulig
  • Toni A. Steiner
  • Hideaki Shimada
  • Krupali Patel
  • Eric Park
  • Ernest S. Kim
  • Jeffrey T. Borenstein
  • Craig M. Neville
  • Bradley T. Keller
Original Article

Abstract

Background

Hepatic stellate cells (HSC) play a major role in the progression of liver fibrosis.

Aim

The aim of our study was to investigate whether rat HSC cultured on a nanofiber membrane (NM) retain their quiescent phenotype during both short- and long-term culture and whether activated HSC revert to a quiescent form when re-cultured on NM.

Methods

Rat HSC cultured for 1 day on plastic plates (PP) were used as quiescent HSC, while cells cultured for 1 week on PP were considered to be activated HSC. Quiescent or activated HSC were subsequently plated on PP or NM and cultured for an additional 4 days at which time their gene expression, stress fiber development, and growth factor production were determined. For long-term culture, HSC were grown on NM for 20 days and the cells then replated on PP and cultured for another 10 days.

Results

Expression of marker genes for HSC activation, stress fiber development, and growth factor production were significantly lower in both quiescent and activated HSC cultured on NM than in those cultured on PP. After long-term culture on NM, activation marker gene expression and stress fiber development were still significantly lower in HSC than in PP, and HSC still retained the ability to activate when replated onto PP.

Conclusions

HSC cultured on NM retained quiescent characteristics after both short- and long-term culture while activated HSC reverted toward a quiescent state when cultured on NM. Cultures of HSC grown on NM are a useful in vitro model to investigate the mechanisms of activation and deactivation.

Keywords

Hepatic stellate cell  Nanofiber membrane Stress fiber Growth factor Quiescent 

Notes

Acknowledgments

This work is supported by Pfizer Inc.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Hiroyuki Eda
    • 1
    • 5
    Email author
  • Katherine M. Kulig
    • 2
  • Toni A. Steiner
    • 1
  • Hideaki Shimada
    • 1
  • Krupali Patel
    • 1
  • Eric Park
    • 3
  • Ernest S. Kim
    • 4
  • Jeffrey T. Borenstein
    • 4
  • Craig M. Neville
    • 2
  • Bradley T. Keller
    • 1
  1. 1.Discovery Biology, St. Louis LaboratoriesPfizer Global Research & Development, Pfizer Inc.ChesterfieldUSA
  2. 2.Center for Regenerative Medicine, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  3. 3.Research Technology CenterPfizer Global Research & Development, Pfizer Inc.CambridgeUSA
  4. 4.The Charles Stark Draper Laboratory, Inc.CambridgeUSA
  5. 5.Exploratory Research LaboratoriesAjinomoto Pharmaceuticals Co. Ltd.KawasakiJapan

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