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    Influence of a 3D microarray environment on human cell culture in drug screening systems

    Author
    Meli, L.; Jordan, E.T.; Clark, D.; Linhardt, Robert J.; Dordick, J.S.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    INFLUENCE OF A THREE-DIMENSIONAL, MICROARRAY ENVIRONMENT ON.pdf (987.0Kb)
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    Date Issued
    2012
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Influence of a 3D microarray environment on human cell culture in drug screening systems, L. Meli, E. T. Jordan, D. Clark, R. J. Linhardt, J. S. Dordick, Biomaterials, 33, 9087-9096, 2012.
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    URI
    https://hdl.handle.net/20.500.13015/5305; https://doi.org/10.1016/j.biomaterials.2012.08.065
    Abstract
    We have used a modified 3D cellular microarray platform for the high-throughput analysis of growth, cytotoxicity, and protein expression profile of a human hepatocellular carcinoma cell line, HepG2, in alginate. The results obtained were compared to analogous studies in 2D and 3D environments at the microtiter scale. The antiproliferative effects of four drugs, tamoxifen, 5-fluorouracil, doxorubicin, and amitriptyline, were studied as a function of seeding density in the three different culture platforms. The chemosensitivity of HepG2 cells to all four compounds decreased substantially with increasing cell number in the 2D and 3D microtiter-based cultures, while no seeding density dependence was observed in the IC50 values obtained in the 3D microarray culture platform. These results can be rationalized based on the development of confluence-dependent resistance in cultures where proliferation is restricted by cell–cell contacts and nutrient availability, as is the case for both of the microtiter-based cultures. Additionally, further development of an on-chip, in-cell immunofluorescence assay provided quantitative data on the levels of specific target proteins involved in proliferation, adhesion, angiogenesis and drug metabolism, and was used to compare expression profiles between 2D and 3D environments. The up-regulation of several CYP450 enzymes, β1-integrin and vascular endothelial growth factor (VEGF) in the 3D microarray cultures suggests that this platform provides a more in vivo-like environment allowing cells to approach their natural phenotype.;
    Description
    Biomaterials, 33, 9087-9096; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    Elsevier
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; https://harc.rpi.edu/;
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    A full text version is available in DSpace@RPI;
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