期刊
BIOTECHNOLOGY JOURNAL
卷 6, 期 2, 页码 204-212出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/biot.201000340
关键词
Cell patterning; 3D ovarian coculture cancer model; Drug screening; High throughput
资金
- Randolph Hearst Foundation
- Department of Medicine, Brigham and Women's Hospital for the Young Investigators in Medicine
- Wellman Center for Photomedicine
- National Institutes of Health [5R01CA119388-03, P01CA084203-06, R21 (EB007707)]
- Center for Integration of Medicine and Innovative Technology (CIMIT) under US Army Medical Research
In vitro 3D cancer models that provide a more accurate representation of disease in vivo are urgently needed to improve our understanding of cancer pathology and to develop better cancer therapies. However, development of 3D models that are based on manual ejection of cells from micropipettes suffer from inherent limitations such as poor control over cell density, limited repeatability, low throughput, and, in the case of coculture models, lack of reproducible control over spatial distance between cell types (e.g., cancer and stromal cells). In this study, we build on a recently introduced 3D model in which human ovarian cancer (OVCAR-5) cells overlaid on Matrigel (TM) spontaneously form multicellular acini. We introduce a high-throughput automated cell printing system to bioprint a 3D coculture model using cancer cells and normal fibroblasts micropatterned on Matrigel (TM). Two cell types were patterned within a spatially controlled microenvironment (e.g., cell density, cell-cell distance) in a high-throughput and reproducible manner; both cell types remained viable during printing and continued to proliferate following patterning. This approach enables the miniaturization of an established macro-scale 3D culture model and would allow systematic investigation into the multiple unknown regulatory feedback mechanisms between tumor and stromal cells and provide a tool for high-throughput drug screening.
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