Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats

Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies...

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Autores principales: Natalia Yudintceva, Ekaterina Lomert, Natalia Mikhailova, Elena Tolkunova, Nikol Agadzhanian, Konstantin Samochernych, Gabriele Multhoff, Grigoriy Timin, Vyacheslav Ryzhov, Vladimir Deriglazov, Anton Mazur, Maxim Shevtsov
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:649f9989d9be43f0ae1633d80e57d8452021-11-25T16:49:25ZTargeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats10.3390/biomedicines91115922227-9059https://doaj.org/article/649f9989d9be43f0ae1633d80e57d8452021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1592https://doaj.org/toc/2227-9059Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (<i>NLR-M</i><sub>2</sub>) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.Natalia YudintcevaEkaterina LomertNatalia MikhailovaElena TolkunovaNikol AgadzhanianKonstantin SamochernychGabriele MulthoffGrigoriy TiminVyacheslav RyzhovVladimir DeriglazovAnton MazurMaxim ShevtsovMDPI AGarticlemesenchymal stem cellsbiodistributionnonlinear magnetic responsesuperparamagnetic iron oxide nanoparticlesmultiforme glioblastomaC6 gliomaBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1592, p 1592 (2021)
institution DOAJ
collection DOAJ
language EN
topic mesenchymal stem cells
biodistribution
nonlinear magnetic response
superparamagnetic iron oxide nanoparticles
multiforme glioblastoma
C6 glioma
Biology (General)
QH301-705.5
spellingShingle mesenchymal stem cells
biodistribution
nonlinear magnetic response
superparamagnetic iron oxide nanoparticles
multiforme glioblastoma
C6 glioma
Biology (General)
QH301-705.5
Natalia Yudintceva
Ekaterina Lomert
Natalia Mikhailova
Elena Tolkunova
Nikol Agadzhanian
Konstantin Samochernych
Gabriele Multhoff
Grigoriy Timin
Vyacheslav Ryzhov
Vladimir Deriglazov
Anton Mazur
Maxim Shevtsov
Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
description Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (<i>NLR-M</i><sub>2</sub>) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.
format article
author Natalia Yudintceva
Ekaterina Lomert
Natalia Mikhailova
Elena Tolkunova
Nikol Agadzhanian
Konstantin Samochernych
Gabriele Multhoff
Grigoriy Timin
Vyacheslav Ryzhov
Vladimir Deriglazov
Anton Mazur
Maxim Shevtsov
author_facet Natalia Yudintceva
Ekaterina Lomert
Natalia Mikhailova
Elena Tolkunova
Nikol Agadzhanian
Konstantin Samochernych
Gabriele Multhoff
Grigoriy Timin
Vyacheslav Ryzhov
Vladimir Deriglazov
Anton Mazur
Maxim Shevtsov
author_sort Natalia Yudintceva
title Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
title_short Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
title_full Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
title_fullStr Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
title_full_unstemmed Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
title_sort targeting brain tumors with mesenchymal stem cells in the experimental model of the orthotopic glioblastoma in rats
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/649f9989d9be43f0ae1633d80e57d845
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