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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Main Authors:	María C. Rosales Gerpe, Jacob P. van Vloten, Lisa A. Santry, Jondavid de Jong, Robert C. Mould, Adrian Pelin, John C. Bell, Byram W. Bridle, Sarah K. Wootton
Format:	Article
Language:	English
Published:	Elsevier 2018-09-01
Series:	Molecular Therapy: Methods & Clinical Development
Online Access:	http://www.sciencedirect.com/science/article/pii/S2329050118300743

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spelling	doaj-b9967c7ee3b74634af0e22890f67f2c82020-11-25T02:27:32ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-09-0110245256Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic TherapyMaría C. Rosales Gerpe0Jacob P. van Vloten1Lisa A. Santry2Jondavid de Jong3Robert C. Mould4Adrian Pelin5John C. Bell6Byram W. Bridle7Sarah K. Wootton8Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaOttawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, CanadaOttawa Hospital Research Institute, Centre for Innovative Cancer Research, Ottawa, ON K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, CanadaDepartment of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada; Corresponding author: Sarah Wootton, Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada.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.http://www.sciencedirect.com/science/article/pii/S2329050118300743
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	María C. Rosales Gerpe Jacob P. van Vloten Lisa A. Santry Jondavid de Jong Robert C. Mould Adrian Pelin John C. Bell Byram W. Bridle Sarah K. Wootton
spellingShingle	María C. Rosales Gerpe Jacob P. van Vloten Lisa A. Santry Jondavid de Jong Robert C. Mould Adrian Pelin John C. Bell Byram W. Bridle Sarah K. Wootton Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and Viral Vectors for Gene and Oncolytic Therapy Molecular Therapy: Methods & Clinical Development
author_facet	María C. Rosales Gerpe Jacob P. van Vloten Lisa A. Santry Jondavid de Jong Robert C. Mould Adrian Pelin John C. Bell Byram W. Bridle Sarah K. Wootton
author_sort	María C. Rosales Gerpe
title	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_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_sort	use of precision-cut lung slices as an ex vivo tool for evaluating viruses and viral vectors for gene and oncolytic therapy
publisher	Elsevier
series	Molecular Therapy: Methods & Clinical Development
issn	2329-0501
publishDate	2018-09-01
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.
url	http://www.sciencedirect.com/science/article/pii/S2329050118300743
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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

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