<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>An attractive approach in the study of human cancers is the use of transparent zebrafish (<italic>Danio rerio</italic>) embryos, which enable the visualization of cancer progression in a living animal.</p></sec><sec><h3>Materials and methods</h3><p>We implanted mixtures of fluorescently labeled glioblastoma (GBM) cells and bonemarrow-derived mesenchymal stem cells (MSCs) into zebrafish embryos to study the cellular pathways of their invasion and the interactions between these cells <italic>in vivo</italic>.</p></sec><sec><h3>Results</h3><p>By developing and applying a carbocyanine-dye-compatible clearing protocol for observation of cells in deep tissues, we showed that U87 and U373 GBM cells rapidly aggregated into tumor masses in the ventricles and midbrain hemispheres of the zebrafish embryo brain, and invaded the central nervous system, often using the ventricular system and the central canal of the spinal cord. However, the GBM cells did not leave the central nervous system. With co-injection of differentially labeled cultured GBM cells and MSCs, the implanted cells formed mixed tumor masses in the brain. We observed tight associations between GBM cells and MSCs, and possible cell-fusion events. GBM cells and MSCs used similar invasion routes in the central nervous system.</p></sec><sec><h3>Conclusions</h3><p>This simple model can be used to study the molecular pathways of cellular processes in GBM cell invasion, and their interactions with various types of stromal cells in double or triple cell co-cultures, to design anti-GBM cell therapies that use MSCs as vectors.</p></sec></abstract>

BackgroundAn attractive approach in the study of human cancers is the use of transparent zebrafish (Danio rerio) embryos, which enable the visualization of cancer progression in a living animal.Materials and methodsWe implanted mixtures of fluorescently labeled glioblastoma (GBM) cells and bonemarrow-derived mesenchymal stem cells (MSCs) into zebrafish embryos to study the cellular pathways of their invasion and the interactions between these cells in vivo.ResultsBy developing and applying a carbocyanine-dye-compatible clearing protocol for observation of cells in deep tissues, we showed that U87 and U373 GBM cells rapidly aggregated into tumor masses in the ventricles and midbrain hemispheres of the zebrafish embryo brain, and invaded the central nervous system, often using the ventricular system and the central canal of the spinal cord. However, the GBM cells did not leave the central nervous system. With co-injection of differentially labeled cultured GBM cells and MSCs, the implanted cells formed mixed tumor masses in the brain. We observed tight associations between GBM cells and MSCs, and possible cell-fusion events. GBM cells and MSCs used similar invasion routes in the central nervous system.ConclusionsThis simple model can be used to study the molecular pathways of cellular processes in GBM cell invasion, and their interactions with various types of stromal cells in double or triple cell co-cultures, to design anti-GBM cell therapies that use MSCs as vectors.

Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish <italic>(Danio rerio)</italic> embryonic brain

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia

Jozef Stefan International Postgraduate School, Ljubljana, Slovenia

Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia

Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia

Radiology and Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish  embryonic brain

BackgroundAn attractive approach in the study of human cancers is the use of transparent zebrafish (Danio rerio) embryos, which enable the visualization of...

Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish (Danio rerio) embryonic brain

Article Category: Research Article

Pubblicato online: 26 mar 2016

Pagine: 159 - 167

Ricevuto: 03 dic 2015

Accettato: 07 feb 2016

DOI: https://doi.org/10.1515/raon-2016-0017

© 2016 Radiol Oncol

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.