Back to Journals » International Journal of Nanomedicine » Volume 12

Human mesenchymal stem cell-derived iron oxide exosomes allow targeted ablation of tumor cells via magnetic hyperthermia

Authors Altanerova U, Babincova M, Babinec P, Benejova K, Jakubechova J, Altanerova V, Zduriencikova M, Repiska V, Altaner C

Received 28 June 2017

Accepted for publication 9 September 2017

Published 27 October 2017 Volume 2017:12 Pages 7923—7936

DOI https://doi.org/10.2147/IJN.S145096

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Video abstract presented by Altanerova et al

Views: 61

U Altanerova,1 M Babincova,2 P Babinec,2 K Benejova,1 J Jakubechova,1 V Altanerova,1 M Zduriencikova,3 V Repiska,4 C Altaner1,3

1Stem Cell Preparation Department, St Elisabeth Cancer Institute, Bratislava, Slovakia; 2Department of Nuclear Physics and Biophysics, Comenius University, Bratislava, Slovakia; 3Cancer Research Institute, Biomedical Center, Slovak Academy of Sciences, Bratislava, Slovakia; 4Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovakia


Abstract: Magnetic hyperthermia, or the heating of tissues using magnetic materials, is a promising approach for treating cancer. We found that human mesenchymal stem cells (MSCs) isolated from various tissues and MSCs expressing the yeast cytosine deaminase::uracil phosphoribosyl transferase suicide fusion gene (yCD::UPRT) can be labeled with Venofer, an iron oxide carbohydrate nanoparticle. Venofer labeling did not affect cell proliferation or the ability to home to tumors. All Venofer-labeled MSCs released exosomes that contained iron oxide. Furthermore, these exosomes were efficiently endocytosed by tumor cells. Exosomes from Venofer-labeled MSCs expressing the yCD::UPRT gene in the presence of the prodrug 5-fluorocytosine inhibited tumor growth in a dose-dependent fashion. The treated tumor cells were also effectively ablated following induction of hyperthermia using an external alternating magnetic field. Cumulatively, we found that magnetic nanoparticles packaged into MSC exosomes are efficiently endocytosed by tumor cells, facilitating targeted tumor cell ablation via magnetically induced hyperthermia.

Keywords: mesenchymal stem cells, iron oxide labeling, Venofer, yCD::UPRT-exosomes, yCD::UPRT-MSCs/Fe exosomes, magnetic hyperthermia

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]