Connective-Tissue Fibroblasts Established on Micropillar Interfaces are Pivotal for Epithelial-Tissue Morphogenesis

Authors

  • Eva Mussig,

    1. Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
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  • Thorsten Steinberg,

    Corresponding author
    1. Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
    • Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany).
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  • Simon Schulz,

    1. Department of Biophysical Chemistry, University of Heidelberg Im Neuenheimer Feld 253, 69120 Heidelberg (Germany)
    2. Max Planck Institute for Metals Research Heisenbergstr. 3, D-70569 Stuttgart (Germany)
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  • Joachim P. Spatz,

    1. Department of Biophysical Chemistry, University of Heidelberg Im Neuenheimer Feld 253, 69120 Heidelberg (Germany)
    2. Max Planck Institute for Metals Research Heisenbergstr. 3, D-70569 Stuttgart (Germany)
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  • Jens Ulmer,

    1. Max Planck Institute for Metals Research Heisenbergstr. 3, D-70569 Stuttgart (Germany)
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  • Niels Grabe,

    1. Department of Medical Informatics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
    2. Hamamatsu TIGA Center, BIOQUANT, University of Heidelberg Im Neuenheimer Feld 267, 69120 Heidelberg (Germany)
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  • Annette Kohl,

    1. Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
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  • Gerda Komposch,

    1. Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
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  • Pascal Tomakidi

    1. Department of Orthodontics and Dentofacial Orthopaedics, University of Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg (Germany)
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Errata

This article is corrected by:

  1. Errata: Connective-Tissue Fibroblasts Established on Micropillar Interfaces are Pivotal for Epithelial-Tissue Morphogenesis Volume 18, Issue 21, Article first published online: 4 November 2008

  • This work is dedicated to Professor Norbert Fusenig in appreciation of his excellent leadership as head of the “Department of Differentiation and Carcinogenesis” of the German Cancer Research Center.

  • E.M. and T.S. contributed equally to this manuscript. We are grateful for financial support provided by the Dietmar-Hopp-Stiftung, GmbH, St. Leon-Rot, Förderbereich Medizin (grant 12/2005 and grant 01/2008 to Thorsten Steinberg and Pascal Tomakidi). Additional financial support has been supplied by the Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde (DGZMK) (grant 11/2006) and the Medical Faculty of the University of Heidelberg (Gerok position) to Eva Mussig. This work has also been implemented in the “BIOQUANT” Research Network of the University of Heidelberg, Germany.

Abstract

Polydimethylsiloxane (PDMS) pillar arrays are applied as a biomechanical microenvironment to establish gingival connective-tissue fibroblasts (GCTFs) and to further analyze the pivotal role of GCTFs in epithelial-tissue morphogenesis. GCTFs are known to exert successful adhesion and growth on fibronectin immobilized on pillar heads, over time, concomitant with the increased gene expression of vimentin and collagen type-I. GCTF-populated pillar arrays clearly reveal that epithelial-tissue morphogenesis of immortalized human gingival keratinocytes (IHGKs), co-cultured for 7 and 14 days, parallels the in vivo phenotype more closely, when compared with GCTF-free control arrays. This in vivo-like phenotype is substantiated by higher mRNA levels for keratin 1, involucrin and filaggrin differentiation markers. Furthermore, it is reflected by a tissue-specific protein orientation of the aforementioned molecules, and also of the cell-to-cell contact forming desmoplakin and the basement membrane constituents, laminin-5, laminin-1/10, and collagen type-IV. These experiments suggest that the in vivo-like phenotype of the IHGK is governed by the GCTFs growing on the micropillar interfaces. Moreover, they form the basis for the optimization or neogeneration of biomaterials by varying predefined microenvironmetal parameters to achieve an in vivo-like cell growth and differentiation, indispensable for tissue morphogenesis during regeneration.

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