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Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro

Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfu...

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Autores principales: La Rocca, Alessia, De Gregorio, Vincenza, Lagreca, Elena, Vecchione, Raffaele, Netti, Paolo Antonio, Imparato, Giorgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059762/
https://www.ncbi.nlm.nih.gov/pubmed/36982752
http://dx.doi.org/10.3390/ijms24065678
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author La Rocca, Alessia
De Gregorio, Vincenza
Lagreca, Elena
Vecchione, Raffaele
Netti, Paolo Antonio
Imparato, Giorgia
author_facet La Rocca, Alessia
De Gregorio, Vincenza
Lagreca, Elena
Vecchione, Raffaele
Netti, Paolo Antonio
Imparato, Giorgia
author_sort La Rocca, Alessia
collection PubMed
description Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer–ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery.
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spelling pubmed-100597622023-03-30 Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro La Rocca, Alessia De Gregorio, Vincenza Lagreca, Elena Vecchione, Raffaele Netti, Paolo Antonio Imparato, Giorgia Int J Mol Sci Article Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded onto porous biodegradable gelatin microbeads (GPMs) and were continuously induced to synthesize and assemble their own ECMs (3D Stroma μTs) in a spinner flask bioreactor. Then, human colon cancer cells were dynamically seeded onto the 3D Stroma μTs to achieve the 3D CRC μTs. Morphological characterization of the 3D CRC μTs was performed to assess the presence of different complex macromolecular components that feature in vivo in the ECM. The results showed the 3D CRC μTs recapitulated the TME in terms of ECM remodeling, cell growth, and the activation of normal fibroblasts toward an activated phenotype. Then, the microtissues were assessed as a drug screening platform by evaluating the effect of 5-Fluorouracil (5-FU), curcumin-loaded nanoemulsions (CT-NE-Curc), and the combination of the two. When taken together, the results showed that our microtissues are promising in that they can help clarify complex cancer–ECM interactions and evaluate the efficacy of therapies. Moreover, they may be combined with tissue-on-chip technologies aimed at addressing further studies in cancer progression and drug discovery. MDPI 2023-03-16 /pmc/articles/PMC10059762/ /pubmed/36982752 http://dx.doi.org/10.3390/ijms24065678 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
La Rocca, Alessia
De Gregorio, Vincenza
Lagreca, Elena
Vecchione, Raffaele
Netti, Paolo Antonio
Imparato, Giorgia
Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title_full Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title_fullStr Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title_full_unstemmed Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title_short Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro
title_sort colorectal cancer bioengineered microtissues as a model to replicate tumor-ecm crosstalk and assess drug delivery systems in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059762/
https://www.ncbi.nlm.nih.gov/pubmed/36982752
http://dx.doi.org/10.3390/ijms24065678
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