title: A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform.
abstract: 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™ spontaneously form multicellular acini. We introduce a high-throughput automated cell printing system to bioprint a 3D coculture model using cancer cells and normal fi broblasts micropatterned on Matrigel™ . 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.
authors.affiliation: Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Celli
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Imran
authors.initials: I
authors.lastname: Rizvi
authors.affiliation: Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Sangjun
authors.initials: S
authors.lastname: Moon
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.affiliation: Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA.
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006801:Humans; D008853:Microscopy; D010051:Ovarian Neoplasms / Q000175:diagnosis*