Neural precursors exhibit distinctly different patterns of cell migration upon transplantation during either the acute or chronic phase of EAE: A serial MR imaging study

Muja, Naser; Cohen, Moshe-Ishay; Zhang, Jiangyang; Kim, Heechul; Gilad, Assaf A.; Walczak, Piotr; Ben‐Hur, Tamir; Bulte, Jeff W.M.

doi:10.1002/mrm.22757

Cited by 30 publications

(21 citation statements)

References 44 publications

(56 reference statements)

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“…Recently, ICV transplanted NPCs were also shown to target the perivascular niche. Although cell migration was evident mostly in white matter tracts, cells also migrated in a radial fashion toward the cortex, along inflamed blood vessels [97]. Thus, transplanted NPCs may exhibit combined immunomodulatory, trophic, and regenerative properties in the involved white matter tracts, as well as at the perivascular spaces, which serve as junctions of inflammatory cell trafficking.…”

Section: Route Of Cell Deliverymentioning

confidence: 99%

“…Recruitment and mobilization of OPCs and multipotential neural precursors in the models of MS have been mainly attributed to the inflammatory process. Brain inflammation attracts the migration of both endogenous [57] and transplanted [94][95][96][97] precursor cells. Various inflammatory cytokines can induce neural/oligodendrocyte precursor cell migration.…”

Section: Myelin Regeneration Fails In Msmentioning

confidence: 99%

“…In the CNS, NPC-mediated bystander immune regulation may take place in the ventricular space and white matter tracts [176], as well as at the level of the atypical perivascular niches [97,152,173]. Following systemic delivery, immune regulation by NPCs occurs in secondary lymphoid organs, such as the lymph nodes [177] or the spleen [178].…”

Section: Immune Modulationmentioning

confidence: 99%

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Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

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Section: Route Of Cell Deliverymentioning

confidence: 99%

Section: Myelin Regeneration Fails In Msmentioning

confidence: 99%

Section: Immune Modulationmentioning

confidence: 99%

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Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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“…Labeling cells with magnetic nanoparticles (MNPs) has been shown to induce sufficient contrast for magnetic resonance imaging (MRI) of cells in the brain [11][12][13][14][15]. Therefore, MRI, in combination with other in vivo molecular imaging techniques, like PET, can provide insights into different cellular processes, including localization and migration of the cells, cell survival and proliferation kinetics, and cell differentiation patterns, which can aid clinical implementation of cell therapy [16].…”

Section: Introductionmentioning

confidence: 99%

Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain

Ramos-Gómez¹,

Seiz²,

Martínez‐Serrano³

2016

Nano Online

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Background: Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. Results: In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. Conclusions: These findings support the use of commercial MNPs to track cells for short-and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

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“…As a consequence, positive contrast techniques generate hyperintensities in neighboring image pixels where the needed phase and frequency conditions are met. However, many labeled cells are required to gain a magnetic field pattern exceeding the cell containing voxel, which in turn precludes the single cell detection needed for in vivo cell migration studies (25).…”

Section: Introductionmentioning

confidence: 99%

Positive contrast of SPIO‐labeled cells by off‐resonant reconstruction of 3D radial half‐echo bSSFP

Liebmann

Neumayer²,

Reinisch

et al. 2014

NMR in Biomedicine

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This article describes a new acquisition and reconstruction concept for positive contrast imaging of cells labeled with superparamagnetic iron oxides (SPIOs). Overcoming the limitations of a negative contrast representation as gained with gradient echo and fully balanced steady state (bSSFP), the proposed method delivers a spatially localized contrast with high cellular sensitivity not accomplished by other positive contrast methods. Employing a 3D radial bSSFP pulse sequence with half-echo sampling, positive cellular contrast is gained by adding artificial global frequency offsets to each half-echo before image reconstruction. The new contrast regime is highlighted with numerical intravoxel simulations including the point-spread function for 3D half-echo acquisitions. Furthermore, the new method is validated on the basis of in vitro cell phantom measurements on a clinical MRI platform, where the measured contrast-to-noise ratio (CNR) of the new approach exceeds even the negative contrast of bSSFP. Finally, an in vivo proof of principle study based on a mouse model with a clear depiction of labeled cells within a subcutaneous cell islet containing a cell density as low as 7 cells/mm(3) is presented. The resultant isotropic images show robustness to motion and a high CNR, in addition to an enhanced specificity due to the positive contrast of SPIO-labeled cells.

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Neural precursors exhibit distinctly different patterns of cell migration upon transplantation during either the acute or chronic phase of EAE: A serial MR imaging study

Cited by 30 publications

References 44 publications

Cell Therapy for Multiple Sclerosis

Cell Therapy for Multiple Sclerosis

Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain

Positive contrast of SPIO‐labeled cells by off‐resonant reconstruction of 3D radial half‐echo bSSFP

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