Effectiveness of micron‐sized superparamagnetic iron oxide particles as markers for detection of migration of bone marrow‐derived mesenchymal stromal cells in a stroke model

Tarulli, Emidio; Chaudhuri, Joydeep D.; Gretka, Voytek; Hoyles, Amy; Morshead, Cindi M.; Stanisz, Greg J.

doi:10.1002/jmri.23897

Cited by 20 publications

(21 citation statements)

References 52 publications

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“…and i.v. administration in animal models of ischemic stroke with different degrees of success in terms of outcome373839 and brain engraftment23404142, but only a few have established a relationship between them434445. In this study, we administered MSCs labeled with D-MNPs to address the relationship between cell allocation and animal recovery after stroke.…”

Section: Discussionmentioning

confidence: 99%

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Argibay

Trekker

Himmelreich

et al. 2017

Sci Rep

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Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

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Section: Discussionmentioning

confidence: 99%

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Argibay

Trekker

Himmelreich

et al. 2017

Sci Rep

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“…In this study, we clearly observed hypointense voxels within the flank tumors of animals injected with FTDlabeled BMSCs and NSCs. Since the SPION labeling does not permit distinction of labeled cells and T 2 * shortening caused by hemorrhages within the tumor (7,21,41), the cell infusions and MR images were taken before the tumors became necrotic in the core. In addition, due to the possibility of activated macrophages engulfing infused cells (37) and become PB positive, the tumor tissues were double-stained with PB and F4/80 to confirm the homing of FTD-labeled stem cells in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, all SPION- and MPIO-labeled cells appear as hypointense voxels on T2* weighted images, and are difficult to differentiate from hemorrhage or heme by-products. Also, the magnetic label from dead or apoptotic cells can be phagocytosed by macrophages and microglia, confounding image interpretation (21). …”

Section: Introductionmentioning

confidence: 99%

Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking

Kim

Lewis

Steiner

et al. 2015

Contrast Media & Molecular

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To develop effective stem cell therapies, it is important to track therapeutic cells non-invasively and monitor homing to areas of pathology. The purpose of this study was to (1) design and evaluate the labeling efficiency of commercially available dextran-coated superparamagnetic iron oxide nanoparticles, FeraTrack Direct (FTD), in various stem and immune cells; (2) assess cytotoxicity and tolerability of the FTD in stem cells; and (3) monitor stem cell homing using FTD-labeled bone marrow derived mesenchymal stromal cells (BMSC) and neural stem cells (NSC) in a tumor model by in vivo MRI. The FTD labeled BMSC, NSC, hematopoietic stem cells (HSC), T-lymphocytes, and monocytes effectively without the need for transfection agents, and Prussian blue (PB) staining and transmission electron microscopy (TEM) confirmed intracellular uptake of the agent. The viability, proliferation, and functionality of the labeled cells were minimally or not affected after labeling. When 106 FTD-labeled BMSC or NSC were injected to C6 glioma bearing nude mice, the cells homing to the tumors were detected as hypointense regions within the tumor using 3T clinical MRI up to 10 days post-injection. Histological analysis confirmed the homing of injected cells to the tumor by presence of PB positive cells that are not macrophages. Labeling of stem cells or immune cells with FTD was non-toxic, and should facilitate the translation of this agent to clinical trials for evaluation of trafficking of cells by MRI.

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“…Many groups have reported detection of single cells in MPIO-labeled cells including hepatocytes transplanted into liver (Shapiro, Sharer et al 2006), individual macrophages infiltrating the rejecting transplanted heart (Wu, Ye et al 2006, Ye, Wu et al 2008), single metastatic tumor cells in the brain and liver (Heyn, Ronald et al 2006, Townson, Ramadan et al 2009), as well as in vivo fates of various types of stem cells (Boulland, Leung et al 2012, Tarulli, Chaudhuri et al 2013, Chen, Lu et al 2016). In all these cases the detection limit of MPIO-containing cells critically depends on the MRI resolution.…”

Section: Resultsmentioning

confidence: 99%

Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth

et al. 2017

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Neural progenitors or neuroblasts are produced by precursor cells in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the olfactory bulbs (OB) throughout life. In the OB, these adult born neurons either die or replace existing olfactory interneurons, playing a critical role in the stabilization of OB circuitry. Although several aspects of the addition of new neurons into the OB have been studied, it is unclear whether long-distance activity from the OB can regulate the influx of migrating neuroblasts along the RMS. In this study, iron oxide-assisted MRI was used to track the migration of neuroblasts in combination with reversible naris occlusion to manipulate odorant-induced activity. It was found that decreasing olfactory activity led to a decrease in the rate of neuroblast migration along the RMS. Removal of the naris occlusion led to an increase in migratory rate back to control levels, indicating that olfactory activity has regulatory function on neuroblast migration in the RMS. Blocking odorant activity also led to an arrest in OB growth and re-opening the block led to a rapid re-growth returning the bulb size to control levels. Furthermore, pharmacogenetic elimination of the neuroblasts demonstrated that they were required for re-growth of the bulb following sensory deprivation. Together, these results show that sensory activity, neural migration and OB growth are tightly coupled in an interdependent manner.

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Effectiveness of micron‐sized superparamagnetic iron oxide particles as markers for detection of migration of bone marrow‐derived mesenchymal stromal cells in a stroke model

Abstract: This study suggests that the use of MPIOs as labeling agents are insufficient to conclusively determine the localization of iron within cells in regions of neuronal ischemia and hemorrhage.

Cited by 20 publications

References 52 publications

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking

Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth

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