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A Coculture Based, 3D Bioprinted Ovarian Tumor Model Combining Cancer Cells and Cancer Associated Fibroblasts
Authors:Zakaria Baka  Claire Godier  Laureline Lamy  Abhik Mallick  Varvara Gribova  Agathe Figarol  Lina Bezdetnaya  Alicia Chateau  Zoé Magne  Marie Stiefel  Dounia Louaguef  Philippe Lavalle  Eric Gaffet  Olivier Joubert  Halima Alem
Affiliation:1. Institut Jean Lamour (IJL), Centre National de la Recherche Scientifique (CNRS), UMR 7198, Université de Lorraine, Campus Artem, 2 allée André Guinier, Nancy, 54011 France;2. Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifque (CNRS), UMR 7039, Université de Lorraine, Campus Sciences, Boulevard des Aiguillette, Vandoeuvre-lès-Nancy, 54506 France

Département Recherche, Institut de Cancérologie de Lorraine (ICL), 6 Avenue de Bourgogne, Vandoeuvre-lès-Nancy, 54519 France;3. Institut National de la Santé et de la Recherche Médicale (INSERM) U1121, Biomaterials and Bioengineering, 1 rue Eugène Boeckel, Strasbourg, 67100 France

Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, Strasbourg, 67000 France;4. Institut FEMTO ST, Centre National de la Recherche Scientifique (CNRS), UMR 6174, Université Bourgogne Franche Comté, 15B Avenue des Montboucons, Besançon, F-25000 France;5. Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifque (CNRS), UMR 7039, Université de Lorraine, Campus Sciences, Boulevard des Aiguillette, Vandoeuvre-lès-Nancy, 54506 France;6. Institut National de la Santé et de la Recherche Médicale (INSERM) U1121, Biomaterials and Bioengineering, 1 rue Eugène Boeckel, Strasbourg, 67100 France

Abstract:Ovarian cancer remains a major public health issue due to its poor prognosis. To develop more effective therapies, it is crucial to set-up reliable models that closely mimic the complexity of the ovarian tumor's microenvironment. 3D bioprinting is currently a promising approach to build heterogenous and reproducible cancer models with controlled shape and architecture. However, this technology is still poorly investigated to model ovarian tumors. In this study, a 3D bioprinted ovarian tumor model combining cancer cells (SKOV-3) and cancer associated fibroblasts (CAFs) are described. The resulting tumor models show their ability to maintain cell viability and proliferation. Cells are observed to self-assemble in heterotypic aggregates. Moreover, CAFs are observed to be recruited and to circle cancer cells reproducing an in vivo process taking place in the tumor microenvironment. Interestingly, this approach also shows its ability to rapidly generate a high number of reproducible tumor models that can be subjected to usual characterizations (cell viability and metabolic activity; histology and immunological studies; and real-time imaging). Therefore, these ovarian tumor models can be an interesting tool for high throughput drug screening applications.
Keywords:3D bioprinting  ovarian cancer  preclinical model  tumor microenvironment
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