Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays
Name
Williams-2010-Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays.pdf
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Author(s)
Williams, Courtney M.
Mehta, Geeta
Peyton, Shelly R.
Zeiger, Adam Scott
Van Vliet, Krystyn J.
Griffith, Linda G.
Date Issued
March 2011
Journal
Tissue Engineering. Part A
Publisher
Mary Ann Liebert, Inc.
Citation
Williams, Courtney M. et al. “Autocrine-Controlled Formation and Function of Tissue-Like Aggregates by Primary Hepatocytes in Micropatterned Hydrogel Arrays.” Tissue Engineering Part A 17.7-8 (2011) : 1055-1068. © Mary Ann Liebert, Inc.
Version
Final published version
Abstract
The liver carries out a variety of essential functions regulated in part by autocrine signaling, including hepatocyte-produced growth factors and extracellular matrix (ECM). The local concentrations of autocrine factors are governed by a balance between receptor-mediated binding at the cell surface and diffusion into the local matrix and are thus expected to be influenced by the dimensionality of the cell culture environment. To investigate the role of growth factor and ECM-modulated autocrine signaling in maintaining appropriate primary hepatocyte survival, metabolic functions, and polarity, we created three-dimensional cultures of defined geometry using micropatterned semisynthetic polyethylene glycol–fibrinogen hydrogels to provide a mechanically compliant, nonadhesive material platform that could be modified by cell-secreted factors. We found that in the absence of exogenous peptide growth factors or ECM, hepatocytes retain the epidermal growth factor (EGF) receptor ligands (EGF and transforming growth factor-α) and the proto-oncogenic mesenchymal epithelial transition factor (c-MET) ligand hepatocyte growth factor (HGF), along with fibronectin. Further, hepatocytes cultured in this three-dimensional microenvironment maintained high levels of liver-specific functions over the 10-day culture period. Function-blocking inhibitors of α5β1 or EGF receptor dramatically reduced cell viability and function, suggesting that signaling by both these receptors is needed for in vitro survival and function of hepatocytes in the absence of other exogenous signals.
MIT Department
Massachusetts Institute of Technology. Center for Gynepathology Research
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1089/ten.TEA.2010.0398
