Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Abhishek Umashankar,1,2,* Mandi J Corenblum,1,* Sneha Ray,1,2,* Michel Valdez,3 Eriko S Yoshimaru,3 Theodore P Trouard,3,4 Lalitha Madhavan1,4 1Department of Neurology, 2Neuroscience and Cognitive Science Undergraduate Program, Undergraduate Biology Research Program, 3Department of Biomedical Engin...

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Autores principales:	Umashankar A, Corenblum MJ, Ray S, Valdez M, Yoshimaru ES, Trouard TP, Madhavan L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	MRI Neural stem cells Iron-oxide nanoparticles Molday ION Rhodamine B Transplantation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5610265f5d7c4211b58c61b8a9abeaa1
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spelling	oai:doaj.org-article:5610265f5d7c4211b58c61b8a9abeaa12021-12-02T03:54:16ZEffects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation1178-2013https://doaj.org/article/5610265f5d7c4211b58c61b8a9abeaa12016-04-01T00:00:00Zhttps://www.dovepress.com/effects-of-the-iron-oxide-nanoparticle-molday-ion-rhodamine-b-on-the-v-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Abhishek Umashankar,1,2,* Mandi J Corenblum,1,* Sneha Ray,1,2,* Michel Valdez,3 Eriko S Yoshimaru,3 Theodore P Trouard,3,4 Lalitha Madhavan1,4 1Department of Neurology, 2Neuroscience and Cognitive Science Undergraduate Program, Undergraduate Biology Research Program, 3Department of Biomedical Engineering, 4Evelyn F McKnight Brain Institute, University of Arizona, Tucson, AZ, USA *These authors contributed equally to this work Abstract: An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 µg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 µg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 µg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 µg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68+-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation. Keywords: MRI, neural stem cells, iron oxide nanoparticles, USPIOUmashankar ACorenblum MJRay SValdez MYoshimaru ESTrouard TPMadhavan LDove Medical PressarticleMRINeural stem cellsIron-oxide nanoparticlesMolday ION Rhodamine BTransplantationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1731-1748 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	MRI Neural stem cells Iron-oxide nanoparticles Molday ION Rhodamine B Transplantation Medicine (General) R5-920
spellingShingle	MRI Neural stem cells Iron-oxide nanoparticles Molday ION Rhodamine B Transplantation Medicine (General) R5-920 Umashankar A Corenblum MJ Ray S Valdez M Yoshimaru ES Trouard TP Madhavan L Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
description	Abhishek Umashankar,1,2,* Mandi J Corenblum,1,* Sneha Ray,1,2,* Michel Valdez,3 Eriko S Yoshimaru,3 Theodore P Trouard,3,4 Lalitha Madhavan1,4 1Department of Neurology, 2Neuroscience and Cognitive Science Undergraduate Program, Undergraduate Biology Research Program, 3Department of Biomedical Engineering, 4Evelyn F McKnight Brain Institute, University of Arizona, Tucson, AZ, USA *These authors contributed equally to this work Abstract: An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 µg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 µg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 µg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 µg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68+-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation. Keywords: MRI, neural stem cells, iron oxide nanoparticles, USPIO
format	article
author	Umashankar A Corenblum MJ Ray S Valdez M Yoshimaru ES Trouard TP Madhavan L
author_facet	Umashankar A Corenblum MJ Ray S Valdez M Yoshimaru ES Trouard TP Madhavan L
author_sort	Umashankar A
title	Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
title_short	Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
title_full	Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
title_fullStr	Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
title_full_unstemmed	Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation
title_sort	effects of the iron oxide nanoparticle molday ion rhodamine b on the viability and regenerative function of neural stem cells: relevance to clinical translation
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/5610265f5d7c4211b58c61b8a9abeaa1
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Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

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