Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles

Tammy L Kalber,1,2,* Katherine L Ordidge,1,2,* Paul Southern,3 Michael R Loebinger,1 Panagiotis G Kyrtatos,2,3 Quentin A Pankhurst,3,* Mark F Lythgoe,2,* Sam M Janes1,* 1Lungs for Living Research Centre, UCL Respiratory, University College London, 2UCL Centre for Advanced Biomedical Imaging, Divisi...

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Autores principales:	Kalber TL, Ordidge KL, Southern P, Loebinger MR, Kyrtatos PG, Pankhurst QA, Lythgoe MF, Janes SM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Mesenchymal stem cells SPIOs Hyperthermia MRI tumor therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8e54a594df1c4f0ea9080b85225f341c
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spelling	oai:doaj.org-article:8e54a594df1c4f0ea9080b85225f341c2021-12-02T00:35:53ZHyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles1178-2013https://doaj.org/article/8e54a594df1c4f0ea9080b85225f341c2016-05-01T00:00:00Zhttps://www.dovepress.com/hyperthermia-treatment-of-tumors-by-mesenchymal-stem-cell-delivered-su-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tammy L Kalber,1,2,* Katherine L Ordidge,1,2,* Paul Southern,3 Michael R Loebinger,1 Panagiotis G Kyrtatos,2,3 Quentin A Pankhurst,3,* Mark F Lythgoe,2,* Sam M Janes1,* 1Lungs for Living Research Centre, UCL Respiratory, University College London, 2UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, 3Healthcare Biomagnetics Laboratory, University College London, London, UK *These authors contributed equally to this work Abstract: Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response. Keywords: mesenchymal stem cells, SPIONs, hyperthermia, MRI, tumor therapyKalber TLOrdidge KLSouthern PLoebinger MRKyrtatos PGPankhurst QALythgoe MFJanes SMDove Medical PressarticleMesenchymal stem cellsSPIOsHyperthermiaMRItumor therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1973-1983 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesenchymal stem cells SPIOs Hyperthermia MRI tumor therapy Medicine (General) R5-920
spellingShingle	Mesenchymal stem cells SPIOs Hyperthermia MRI tumor therapy Medicine (General) R5-920 Kalber TL Ordidge KL Southern P Loebinger MR Kyrtatos PG Pankhurst QA Lythgoe MF Janes SM Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
description	Tammy L Kalber,1,2,* Katherine L Ordidge,1,2,* Paul Southern,3 Michael R Loebinger,1 Panagiotis G Kyrtatos,2,3 Quentin A Pankhurst,3,* Mark F Lythgoe,2,* Sam M Janes1,* 1Lungs for Living Research Centre, UCL Respiratory, University College London, 2UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, 3Healthcare Biomagnetics Laboratory, University College London, London, UK *These authors contributed equally to this work Abstract: Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response. Keywords: mesenchymal stem cells, SPIONs, hyperthermia, MRI, tumor therapy
format	article
author	Kalber TL Ordidge KL Southern P Loebinger MR Kyrtatos PG Pankhurst QA Lythgoe MF Janes SM
author_facet	Kalber TL Ordidge KL Southern P Loebinger MR Kyrtatos PG Pankhurst QA Lythgoe MF Janes SM
author_sort	Kalber TL
title	Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
title_short	Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
title_full	Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
title_fullStr	Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
title_full_unstemmed	Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
title_sort	hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/8e54a594df1c4f0ea9080b85225f341c
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Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles

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