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A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma-Toward a Better Mimicry of the in vivo Tumor Microenvironment

Gupta, P; Pérez-Mancera, PA; Kocher, H; Nisbet, A; Schettino, G; Velliou, EG; (2020) A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma-Toward a Better Mimicry of the in vivo Tumor Microenvironment. Frontiers in Bioengineering and Biotechnology , 8 , Article 290. 10.3389/fbioe.2020.00290. Green open access

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Abstract

With a very low survival rate, pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. This has been primarily attributed to (i) its late diagnosis and (ii) its high resistance to current treatment methods. The latter specifically requires the development of robust, realistic in vitro models of PDAC, capable of accurately mimicking the in vivo tumor niche. Advancements in the field of tissue engineering (TE) have helped the development of such models for PDAC. Herein, we report for the first time a novel hybrid, polyurethane (PU) scaffold-based, long-term, multicellular (tri-culture) model of pancreatic cancer involving cancer cells, endothelial cells, and stellate cells. Recognizing the importance of ECM proteins for optimal growth of different cell types, the model consists of two different zones/compartments: an inner tumor compartment consisting of cancer cells [fibronectin (FN)-coated] and a surrounding stromal compartment consisting of stellate and endothelial cells [collagen I (COL)-coated]. Our developed novel hybrid, tri-culture model supports the proliferation of all different cell types for 35 days (5 weeks), which is the longest reported timeframe in vitro. Furthermore, the hybrid model showed extensive COL production by the cells, mimicking desmoplasia, one of PDAC's hallmark features. Fibril alignment of the stellate cells was observed, which attested to their activated state. All three cell types expressed various cell-specific markers within the scaffolds, throughout the culture period and showed cellular migration between the two zones of the hybrid scaffold. Our novel model has great potential as a low-cost tool for in vitro studies of PDAC, as well as for treatment screening.

Type: Article
Title: A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma-Toward a Better Mimicry of the in vivo Tumor Microenvironment
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fbioe.2020.00290
Publisher version: http://doi.org/10.3389/fbioe.2020.00290
Language: English
Additional information: © 2020 Gupta, Pérez-Mancera, Kocher, Nisbet, Schettino and Velliou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: 3D model, endothelial cells, multicellular tumor model, pancreatic cancer, pancreatic stellate cells, polyurethane scaffold, scaffold-assisted tumor model
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10098543
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