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Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy

Organotypic slice cultures recapitulate many features of an intact organ, including cellular architecture, microenvironment, and polarity, making them an ideal tool for the ex vivo study of viruses and viral vectors. Here, we describe a procedure for generating precision-cut ovine and murine tissue...

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Autores principales: Rosales Gerpe, María C., van Vloten, Jacob P., Santry, Lisa A., de Jong, Jondavid, Mould, Robert C., Pelin, Adrian, Bell, John C., Bridle, Byram W., Wootton, Sarah K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092314/
https://www.ncbi.nlm.nih.gov/pubmed/30112421
http://dx.doi.org/10.1016/j.omtm.2018.07.010
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author Rosales Gerpe, María C.
van Vloten, Jacob P.
Santry, Lisa A.
de Jong, Jondavid
Mould, Robert C.
Pelin, Adrian
Bell, John C.
Bridle, Byram W.
Wootton, Sarah K.
author_facet Rosales Gerpe, María C.
van Vloten, Jacob P.
Santry, Lisa A.
de Jong, Jondavid
Mould, Robert C.
Pelin, Adrian
Bell, John C.
Bridle, Byram W.
Wootton, Sarah K.
author_sort Rosales Gerpe, María C.
collection PubMed
description Organotypic slice cultures recapitulate many features of an intact organ, including cellular architecture, microenvironment, and polarity, making them an ideal tool for the ex vivo study of viruses and viral vectors. Here, we describe a procedure for generating precision-cut ovine and murine tissue slices from agarose-perfused normal and murine melanoma tumor-bearing lungs. Furthermore, we demonstrate that these precision-cut lung slices can be maintained up to 1 month and can be used for a range of applications, which include characterizing the tissue tropism of viruses that cannot be propagated in cell monolayers, evaluating the transducing properties of gene therapy vectors, and, finally, investigating the tumor specificity of oncolytic viruses. Our results suggest that ex vivo lung slices are an ideal platform for studying the tissue specificity and cancer cell selectivity of gene therapy vectors and oncolytic viruses prior to in vivo studies, providing justification for pre-clinical work.
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spelling pubmed-60923142018-08-15 Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy Rosales Gerpe, María C. van Vloten, Jacob P. Santry, Lisa A. de Jong, Jondavid Mould, Robert C. Pelin, Adrian Bell, John C. Bridle, Byram W. Wootton, Sarah K. Mol Ther Methods Clin Dev Article Organotypic slice cultures recapitulate many features of an intact organ, including cellular architecture, microenvironment, and polarity, making them an ideal tool for the ex vivo study of viruses and viral vectors. Here, we describe a procedure for generating precision-cut ovine and murine tissue slices from agarose-perfused normal and murine melanoma tumor-bearing lungs. Furthermore, we demonstrate that these precision-cut lung slices can be maintained up to 1 month and can be used for a range of applications, which include characterizing the tissue tropism of viruses that cannot be propagated in cell monolayers, evaluating the transducing properties of gene therapy vectors, and, finally, investigating the tumor specificity of oncolytic viruses. Our results suggest that ex vivo lung slices are an ideal platform for studying the tissue specificity and cancer cell selectivity of gene therapy vectors and oncolytic viruses prior to in vivo studies, providing justification for pre-clinical work. American Society of Gene & Cell Therapy 2018-08-04 /pmc/articles/PMC6092314/ /pubmed/30112421 http://dx.doi.org/10.1016/j.omtm.2018.07.010 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rosales Gerpe, María C.
van Vloten, Jacob P.
Santry, Lisa A.
de Jong, Jondavid
Mould, Robert C.
Pelin, Adrian
Bell, John C.
Bridle, Byram W.
Wootton, Sarah K.
Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title_full Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title_fullStr Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title_full_unstemmed Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title_short Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy
title_sort use of precision-cut lung slices as an ex vivo tool for evaluating viruses and viral vectors for gene and oncolytic therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092314/
https://www.ncbi.nlm.nih.gov/pubmed/30112421
http://dx.doi.org/10.1016/j.omtm.2018.07.010
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