Magnetic Resonance Imaging of Monocytes Labeled with Ultrasmall Superparamagnetic Particles of Iron Oxide Using Magnetoelectroporation in an Animal Model of Multiple Sclerosis

Engberink, Raoul D. Oude; Pol, Susanne M. A. van der; Walczak, Piotr; Toorn, Annette van der; Viergever, Max A.; Dijkstra, Christine D.; Bulte, Jeff W.M.; Vries, Helga E. de; Blezer, Erwin L. A.

doi:10.2310/7290.2010.00016

Cited by 25 publications

(22 citation statements)

References 26 publications

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“…The cell metabolic activity was assessed with 3-(4,5-dimethylthiazol-2-yl) -5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) using CellTiter 96 AQ ueous one solution cell proliferation assay (Promega, Madison, WI) [20]. Feridex labeling efficacy was determined by counting the labeled cells [21] after Prussian blue staining, while PKH26 labeling efficacy determined by counting labeled cells under a fluorescent microscope.…”

Section: Methodsmentioning

confidence: 99%

MRI of Auto-Transplantation of Bone Marrow-Derived Stem-Progenitor Cells for Potential Repair of Injured Arteries

et al. 2012

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BackgroundThis study was to validate the feasibility of using clinical 3.0T MRI to monitor the migration of autotransplanted bone marrow (BM)-derived stem-progenitor cells (SPC) to the injured arteries of near-human sized swine for potential cell-based arterial repair.MethodologyThe study was divided into two phases. For in vitro evaluation, BM cells were extracted from the iliac crests of 13 domestic pigs and then labeled with a T2 contrast agent, Feridex, and/or a fluorescent tissue marker, PKH26. The viability, the proliferation efficiency and the efficacies of Feridex and/or PKH26 labeling were determined. For in vivo validation, the 13 pigs underwent endovascular balloon-mediated intimal damages of the iliofemoral arteries. The labeled or un-labeled BM cells were autotransplanted back to the same pig from which the BM cells were extracted. Approximately three weeks post-cell transplantation, 3.0T T2-weighted MRI was performed to detect Feridex-created signal voids of the transplanted BM cells in the injured iliofemoral arteries, which was confirmed by subsequent histologic correlation.Principal FindingsOf the in vitro study, the viability of dual-labeled BM cells was 95–98%. The proliferation efficiencies of dual-labeled BM cells were not significantly different compared to those of non-labeled cells. The efficacies of Feridex- and PKH26 labeling were 90% and 100%, respectively. Of the in vivo study, 3.0T MRI detected the auto-transplanted BM cells migrated to the injured arteries, which was confirmed by histologic examinations.ConclusionThis study demonstrates the capability of using clinical 3.0T MRI to monitor the auto-transplantation of BM cells that migrate to the injured arteries of large animals, which may provide a useful MRI technique to monitor cell-based arterial repair.

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Section: Methodsmentioning

confidence: 99%

MRI of Auto-Transplantation of Bone Marrow-Derived Stem-Progenitor Cells for Potential Repair of Injured Arteries

et al. 2012

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“…These agents provide a means to track migration of monocytes into the CNS during EAE and to follow their behaviour as macrophages once in the CNS. In EAE animals, iron nanoparticles have been shown to accumulate in the spinal cord (Chin et al, 2009; Dousset et al, 1999b; Engberink et al, 2010; Millward et al, 2013), brainstem (Chin et al, 2009; Dousset et al, 1999a; Millward et al, 2013; Brochet et al, 2006; Tysiak et al, 2009), cerebellum (Chin et al, 2009; Dousset et al, 1999a; Engberink et al, 2010; Millward et al, 2013; Brochet et al, 2006; Tysiak et al, 2009; Oweida et al, 2007), corpus callosum (Wuerfel et al, 2007), cortex (Wuerfel et al, 2007; Tysiak et al, 2009), choroid plexus (Millward et al, 2013) and vascular endothelium (Millward et al, 2013; Xu et al, 1998). In some studies, Prussian Blue staining for non-heme iron was performed to provide histological confirmation of the presence of iron nanoparticles where MRI had shown hypointense signals (Wuerfel et al, 2007; Chin et al, 2009; Engberink et al, 2010; Millward et al, 2013; Tysiak et al, 2009; Xu et al, 1998).…”

Section: Mri Studies In Animal Models Of Msmentioning

confidence: 99%

Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

Nathoo

Yong

Dunn

2014

NeuroImage: Clinical

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There are exciting new advances in multiple sclerosis (MS) resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR) is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS) studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

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“…As previously mentioned, the association of SPIONs with stem cells offers an attractive method for tracking, targeting and controlling cells [48]. Broadly speaking, this association is achieved through either the internalisation of SPIONs or the binding of SPIONS to cell surface markers (for example, integrins) or to specific antibodies [4,49,50].…”

Section: Labelling Of Stem Cells With Spionsmentioning

confidence: 99%

“…Detection of SPIONs is attributed to the disruption of the magnetic field by the iron core. This disruption can be translated into a loss of signal and can be visualised as a hypointense region on T2 MRI sequences [48]. MRI has a resolution of about 25 to 100 μm resolution [62], which permits tracking of individual cells while still monitoring the surrounding anatomical structures.…”

Section: Tracking Targeting and Activation Of Spion-labelled Cellsmentioning

confidence: 99%

Orthopaedic applications of nanoparticle-based stem cell therapies

2012

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Stem cells have tremendous applications in the field of regenerative medicine and tissue engineering. These are pioneering fields that aim to create new treatments for disease that currently have limited therapies or cures. A particularly popular avenue of research has been the regeneration of bone and cartilage to combat various orthopaedic diseases. Magnetic nanoparticles (MNPs) have been applied to aid the development and translation of these therapies from research to the clinic. This review highlights contemporary research for the applications of iron-oxide-based MNPs for the therapeutic implementation of stem cells in orthopaedics. These MNPs comprise of an iron oxide core, coated with a choice of biological polymers that can facilitate the uptake of MNPs by cells through improving endocytic activity. The combined use of these oxides and the biological polymer coatings meet biological requirements, effectively encouraging the use of MNPs in regenerative medicine. The association of MNPs with stem cells can be achieved via the process of endocytosis resulting in the internalisation of these particles or the attachment to cell surface receptors. This allows for the investigation of migratory patterns through various tracking studies, the targeting of particle-labelled cells to desired locations via the application of an external magnetic field and, finally, for activation stem cells to initiate various cellular responses to induce the differentiation. Characterisation of cell localisation and associated tissue regeneration can therefore be enhanced, particularly for in vivo applications. MNPs have been shown to have the potential to stimulate differentiation of stem cells for orthopaedic applications, without limiting proliferation. However, careful consideration of the use of active agents associated with the MNP is suggested, for differentiation towards specific lineages. This review aims to broaden the knowledge of current applications, paving the way to translate the in vitro and in vivo work into further orthopaedic clinical studies.

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Magnetic Resonance Imaging of Monocytes Labeled with Ultrasmall Superparamagnetic Particles of Iron Oxide Using Magnetoelectroporation in an Animal Model of Multiple Sclerosis

Cited by 25 publications

References 26 publications

MRI of Auto-Transplantation of Bone Marrow-Derived Stem-Progenitor Cells for Potential Repair of Injured Arteries

MRI of Auto-Transplantation of Bone Marrow-Derived Stem-Progenitor Cells for Potential Repair of Injured Arteries

Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

Orthopaedic applications of nanoparticle-based stem cell therapies

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