Local control of hepatic phenotype with growth factor-encoded surfaces

Dipali Patel, Amranul Haque, Caroline N. Jones, Nazgul Tuleouva, Elena Foster, Tam Vu, A Hari Reddi, Alexander Revzin

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The goal of the present study was to modulate the phenotype expression of hepatocytes in vitro on surfaces imprinted with growth factors (GFs). Hepatocyte growth factor (HGF) or transforming-growth factor-β1 (TGF-β1) were mixed with collagen (I) and robotically printed onto standard glass slides to create arrays of 300 μm or 500 μm diameter spots. Primary rat hepatocytes were seeded on top of the arrays, forming clusters corresponding in size to the underlying protein spots. The TGF-β1 spots appeared to downregulate markers of hepatic (epithelial) phenotype while upregulating expression of mesenchymal markers. Conversely, hepatocytes cultured on HGF spots maintained high level of epithelial markers. When hepatocytes were seeded onto alternating spots of HGF and TGF-β1, their phenotype was found to depend on center-to-center distance between the spots. At shorter distances cross-expression of epithelial and mesenchymal markers was observed while at distances exceeding 1.25 mm divergence of phenotypes, epithelial on HGF and mesenchymal on TGF-β was seen. Overall, our results demonstrate that GF-encoded surfaces can modulate phenotype within groups of cells cultured on the same surface. Given the importance of phenotype switching in development, fibrosis and cancer, this platform may be used to gain useful insights into the mechanisms of processes such as epithelial-to-mesenchymal transition or stem cell fate selections.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalIntegrative Biology (United Kingdom)
Volume6
Issue number1
DOIs
StatePublished - Jan 2014

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

Patel, D., Haque, A., Jones, C. N., Tuleouva, N., Foster, E., Vu, T., Reddi, A. H., & Revzin, A. (2014). Local control of hepatic phenotype with growth factor-encoded surfaces. Integrative Biology (United Kingdom), 6(1), 44-52. https://doi.org/10.1039/c3ib40140e