Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays
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...
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| Format: | Article |
| Language: | en_US |
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Mary Ann Liebert, Inc.
2011
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| Online Access: | http://hdl.handle.net/1721.1/64804 https://orcid.org/0000-0001-5735-0560 https://orcid.org/0000-0002-1801-5548 |
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| author | Williams, Courtney M. Mehta, Geeta Peyton, Shelly R. Zeiger, Adam Scott Van Vliet, Krystyn J. Griffith, Linda G. |
| author2 | Massachusetts Institute of Technology. Center for Gynepathology Research |
| author_facet | Massachusetts Institute of Technology. Center for Gynepathology Research Williams, Courtney M. Mehta, Geeta Peyton, Shelly R. Zeiger, Adam Scott Van Vliet, Krystyn J. Griffith, Linda G. |
| author_sort | Williams, Courtney M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:40:54Z |
| format | Article |
| id | mit-1721.1/64804 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:40:54Z |
| publishDate | 2011 |
| publisher | Mary Ann Liebert, Inc. |
| record_format | dspace |
| spelling | mit-1721.1/648042022-10-02T03:23:04Z Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays Williams, Courtney M. Mehta, Geeta Peyton, Shelly R. Zeiger, Adam Scott Van Vliet, Krystyn J. Griffith, Linda G. 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 Van Vliet, Krystyn J. Williams, Courtney M. Mehta, Geeta Peyton, Shelly R. Zeiger, Adam Scott Van Vliet, Krystyn J. Griffith, Linda G. 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. National Institutes of Health (U.S.) (grant NIBIB R01EB003805) National Institute of Environmental Health Sciences (MIT Center for Environmental Health Sciences (P30ES002109)) National Institute of Environmental Health Sciences (MIT Center for Environmental Health Sciences (MIT Center for Environmental Health Sciences (R01ES015241) Ruth L. Kirschstein National Research Service Award (postdoctoral fellowship) National Science Foundation (U.S.) (CAREER Award) National Defense Science and Engineering Graduate Fellowship 2011-07-14T14:03:13Z 2011-07-14T14:03:13Z 2011-03 2010-07 Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X http://hdl.handle.net/1721.1/64804 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. https://orcid.org/0000-0001-5735-0560 https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1089/ten.TEA.2010.0398 Tissue Engineering. Part A 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. application/pdf Mary Ann Liebert, Inc. Mary Ann Liebert |
| spellingShingle | Williams, Courtney M. Mehta, Geeta Peyton, Shelly R. Zeiger, Adam Scott Van Vliet, Krystyn J. Griffith, Linda G. Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title | Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title_full | Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title_fullStr | Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title_full_unstemmed | Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title_short | Autocrine-controlled formation and function of tissue-like aggregates by hepatocytes in micropatterned hydrogel arrays |
| title_sort | autocrine controlled formation and function of tissue like aggregates by hepatocytes in micropatterned hydrogel arrays |
| url | http://hdl.handle.net/1721.1/64804 https://orcid.org/0000-0001-5735-0560 https://orcid.org/0000-0002-1801-5548 |
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