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A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells

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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.

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Acknowledgments

This work is supported by Pfizer Inc.

Conflict of interest

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Authors and Affiliations

  1. Discovery Biology, St. Louis Laboratories, Pfizer Global Research & Development, Pfizer Inc., Chesterfield, MO, USA

    Hiroyuki Eda, Toni A. Steiner, Hideaki Shimada, Krupali Patel & Bradley T. Keller

  2. Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Katherine M. Kulig & Craig M. Neville

  3. Research Technology Center, Pfizer Global Research & Development, Pfizer Inc., Cambridge, MA, USA

    Eric Park

  4. The Charles Stark Draper Laboratory, Inc., Cambridge, MA, USA

    Ernest S. Kim & Jeffrey T. Borenstein

  5. Exploratory Research Laboratories, Ajinomoto Pharmaceuticals Co. Ltd., Kawasaki, Japan

    Hiroyuki Eda

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  1. Hiroyuki Eda
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Correspondence to Hiroyuki Eda.

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Eda, H., Kulig, K.M., Steiner, T.A. et al. A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells. Dig Dis Sci 57, 1152–1162 (2012). https://doi.org/10.1007/s10620-012-2084-9

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  • DOI: https://doi.org/10.1007/s10620-012-2084-9

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