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A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi...

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Autores principales: Candini, Olivia, Grisendi, Giulia, Foppiani, Elisabetta Manuela, Brogli, Matteo, Aramini, Beatrice, Masciale, Valentina, Spano, Carlotta, Petrachi, Tiziana, Veronesi, Elena, Conte, Pierfranco, Mari, Giorgio, Dominici, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509120/
https://www.ncbi.nlm.nih.gov/pubmed/31073193
http://dx.doi.org/10.1038/s41598-019-43613-9
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author Candini, Olivia
Grisendi, Giulia
Foppiani, Elisabetta Manuela
Brogli, Matteo
Aramini, Beatrice
Masciale, Valentina
Spano, Carlotta
Petrachi, Tiziana
Veronesi, Elena
Conte, Pierfranco
Mari, Giorgio
Dominici, Massimo
author_facet Candini, Olivia
Grisendi, Giulia
Foppiani, Elisabetta Manuela
Brogli, Matteo
Aramini, Beatrice
Masciale, Valentina
Spano, Carlotta
Petrachi, Tiziana
Veronesi, Elena
Conte, Pierfranco
Mari, Giorgio
Dominici, Massimo
author_sort Candini, Olivia
collection PubMed
description Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches.
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spelling pubmed-65091202019-05-22 A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology Candini, Olivia Grisendi, Giulia Foppiani, Elisabetta Manuela Brogli, Matteo Aramini, Beatrice Masciale, Valentina Spano, Carlotta Petrachi, Tiziana Veronesi, Elena Conte, Pierfranco Mari, Giorgio Dominici, Massimo Sci Rep Article Tumors develop within complex cell-to-cell interactions, with accessory cells playing a relevant role starting in the early phases of cancer progression. This event occurs in a three-dimensional (3D) environment, which to date, has been difficult to reproduce in vitro due to its complexity. While bi-dimensional cultures have generated substantial data, there is a progressive awareness that 3D culture strategies may rapidly increase the understanding of tumor development and be used in anti-cancer compound screening and for predicting response to new drugs utilizing personalized approaches. However, simple systems capable of rapidly rebuilding cancer tissues ex-vivo in 3D are needed and could be used for a variety of applications. Therefore, we developed a flat, handheld and versatile 3D cell culture bioreactor that can be loaded with tumor and/or normal cells in combination which can be monitored using a variety of read-outs. This biocompatible device sustained 3D growth of tumor cell lines representative of various cancers, such as pancreatic and breast adenocarcinoma, sarcoma, and glioblastoma. The cells repopulated the thin matrix which was completely separated from the outer space by two gas-permeable membranes and was monitored in real-time using both microscopy and luminometry, even after transportation. The device was tested in 3D cytotoxicity assays to investigate the anti-cancer potential of chemotherapy, biologic agents, and cell-based therapy in co-cultures. The addition of luciferase in target cancer cells is suitable for comparative studies that may also involve parallel in vivo investigations. Notably, the system was challenged using primary tumor cells harvested from lung cancer patients as an innovative predictive functional assay for cancer responsiveness to checkpoint inhibitors, such as nivolumab. This bioreactor has several novel features in the 3D-culture field of research, representing a valid tool useful for cancer investigations, drug screenings, and other toxicology approaches. Nature Publishing Group UK 2019-05-09 /pmc/articles/PMC6509120/ /pubmed/31073193 http://dx.doi.org/10.1038/s41598-019-43613-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Candini, Olivia
Grisendi, Giulia
Foppiani, Elisabetta Manuela
Brogli, Matteo
Aramini, Beatrice
Masciale, Valentina
Spano, Carlotta
Petrachi, Tiziana
Veronesi, Elena
Conte, Pierfranco
Mari, Giorgio
Dominici, Massimo
A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title_full A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title_fullStr A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title_full_unstemmed A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title_short A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology
title_sort novel 3d in vitro platform for pre-clinical investigations in drug testing, gene therapy, and immuno-oncology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509120/
https://www.ncbi.nlm.nih.gov/pubmed/31073193
http://dx.doi.org/10.1038/s41598-019-43613-9
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