Magnetic Resonance Imaging Tracking Research Articles

In Vivo Monitoring and Magnetically‐Enhanced Delivery of CAR T‐Cells to Solid Tumor

AbstractChimeric antigen receptor (CAR) T‐cell therapy demonstrates efficacy for the treatment of hematologic cancers, but remains challenging in solid tumors because of the hostile tumor microenvironment and heterogeneity that restrict the infiltration and activity of CAR T‐cells. The lack of clinical imaging methods to monitor CAR T‐cell therapy in patients limits the potential to enhance the therapeutic approach and predict patient response. Here, a straightforward, non‐invasive method for Magnetic Resonance Imaging (MRI) tracking and magnetic targeting of CAR T‐cells to enhance T‐cell trafficking to solid tumors, in a setting that can be deployed in clinics, is reported. Iron oxide nanoparticles are loaded into T‐cells, allowing MRI detection and magnetic cell guidance, while preserving T‐cell viability, functions, and CAR specificity to target epidermal growth factor receptor (EGFR)‐expressing tumors. Longitudinal MRI monitoring of T‐cells over 14 days reveals differences in tumor infiltration rates and antitumor efficacy between EGFR‐targeted CAR T‐cells and non‐transduced T‐cell. Moreover, an external magnet placed over the tumor enhances the infiltration of CAR T‐cells and increases their antitumor effect. MRI monitoring and magnetic guidance represent a dual‐pronged clinically feasible therapeutic strategy to control and promote CAR T‐cells delivery into solid tumors, thereby improving the precision, efficacy, and safety of the treatment.

Viral capsid-mediated efficient cell labeling of micron-sized magnetic particles for highly sensitive long-term in vivo tumor cells MRI tracking

As a contrast agent, micron-sized iron oxide particles (MPIO) offer major advantages for monitoring tumor cells in vivo—applications crucial for studies of tumorigenesis and metastasis. However, labeling tumor cells with MPIO is often dependent on phagocytosis, which limits the labeling efficiency of the cells and thus affects in vivo tumor cell tracking. To address this issue, we prepared a virus-like particle (VLP) consisting of the SV40 VP1 protein modified on the surface of a MPIO (vMPIO). The vMPIO can enter cells via a pathway similar to that of viral infection (caveolae-dependent endocytosis pathway). This approach increased the number of vMPIO in individual labeled cells, which in turn enhances magnetic resonance imaging (MRI) signal intensity and the number of vMPIO in daughter cells. These vMPIO-labeled cells can be detected by MRI in vitro and in vivo even in very small numbers (≤10 cells). Furthermore, vMPIO-labeled cells were successfully applied to long-term tracing of tumor tissue and detection of early metastatic lesions. This VLP-mediated MPIO labeling strategy (vML) not only enables highly sensitive in vivo MRI but also introduces a useful technical tool for investigating tumor invasion and early metastasis.

Potential of predicting mildly reduced and reduced left ventricular ejection fraction in patients in the post-infarction period

Aim. To analyze ischemic and reperfusion injury characteristics, as well as myocardial performance, to identify predictors of reduced left ventricular (LV) ejection fraction (EF) <50% 24 weeks after ST-segment elevation myocardial infarction (STEMI) in patients who underwent revascularization.Material and methods. The study included were 65 patients (age 58 (52; 60) years), who were examined on days 7-10 and after 24 weeks. Based on cardiac magnetic resonance imaging (MRI), parameters of ischemic and reperfusion injury were determined. Speckle tracking echocardiography was used to evaluate the myocardial function.Results. All 65 patients completed the study. Based on echocardiography, patients were divided into following groups: 1 — 45 people with LVEF ≥50%, 2 — 20 patients with LVEF <50%. In patients with LVEF ≥50% 24 weeks after STEMI, there was a decrease in the ischemia injury mass by 32,3% (p=0,001) due to regression of the scar mass by 28% (p=0,008) and the peri-infarct heterogeneous zone by 33,3% (p=0,020). In group 2, the indicators did not change. At the repeat visit, there was a decrease in the number of people with microvascular obstruction in the group of LVEF ≥50% from 44 to 16% (p<0,001), while in LVEF <50% — from 65 to 40% (p=0,045). According to echocardiography, global wasted work in group 1 decreased from 77 (50,5; 105,5) to 59 (43; 92) mm Hg% (p=0,042), while in group 2, it increased from 99,5 (59; 181) to 104,5 (58,5; 156,5) mm Hg% (p=0,765). Global work efficiency and global work index prevailed in patients with LVEF ≥50% at two visits (p<0,05). The following predictors of decreased LVEF were determined 24 weeks after STEMI: ischemia injury mass, scar tissue, microvascular obstruction, global contrast index according to MRI; global work efficiency and global work index on echo cardiography.Conclusion. Contrast-enhanced cardiac MRI and speckle tracking echocardiography are complementary methods that allow quantitative morphofunctional assessment of post-infarction cardiosclerosis and predict the development of mildly reduced and reduced LVEF in the medium term.

Longitudinal Magnetic Resonance Imaging Tracking of Transplanted Neural Progenitor Cells in the Spinal Cord Utilizing the Bright-Ferritin Mechanism.

Human neural progenitor cells (hNPCs) hold promise for treating spinal cord injury. Studies to date have focused on improving their regenerative potential and therapeutic effect. Equally important is ensuring successful delivery and engraftment of hNPCs at the injury site. Unfortunately, no current imaging solution for cell tracking is compatible with long-term monitoring in vivo. The objective of this study was to apply a novel bright-ferritin magnetic resonance imaging (MRI) mechanism to track hNPC transplants longitudinally and on demand in the rat spinal cord. We genetically modified hNPCs to stably overexpress human ferritin. Ferritin-overexpressing (FT) hNPCs labeled with 0.2 mM manganese provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, morphology, proliferation, and differentiation. In vivo, 2 M cells were injected into the cervical spinal cord of Rowett nude rats. MRI employed T1-weighted acquisitions and T1 mapping on a 3 T scanner. Conventional short-term cell tracking was performed using exogenous Mn labeling prior to cell transplantation, which displayed transient bright contrast on MRI 1 day after cell transplantation and disappeared after 1 week. In contrast, long-term cell tracking using bright-ferritin allowed on-demand signal recall upon Mn supplementation and precise visualization of the surviving hNPC graft. In fact, this new cell tracking technology identified 7 weeks post-transplantation as the timepoint by which substantial hNPC integration occurred. Spatial distribution of hNPCs on MRI matched that on histology. In summary, bright-ferritin provides the first demonstration of long-term, on-demand, high-resolution, and specific tracking of hNPCs in the rat spinal cord.

Enhancing stem cell therapy efficacy with functional lignin modified cerium-iron nanozyme through magnetic resonance imaging tracking and apoptosis protection in inflammatory environment

Stem cell transplantation provides a promising approach for addressing inflammation and functional disorders. Nonetheless, the viability of these transplanted cells diminishes significantly within pathological environments, limiting their therapeutic potential. Moreover, the non-invasive tracking of these cells in vivo remains a considerable challenge, hampering the assessment of their therapeutic efficacy. Transition-metal oxide nanocrystals, known for their unique “enzyme-like” catalytic property and imaging capability, provide a new avenue for clinical application. In this study, the lignin as a biocompatible macromolecule was modified with poly (ethylene glycol) through chain-transfer polymerization, and then it was utilized to incorporate superparamagnetic iron oxide and cerium oxide nanocrystals creating a functional nanozyme. The iron oxide nanocrystals self-assembled into the hydrophobic core of nano system, while the in-situ mineralization of cerium oxide particles was carried out with the assistance of peripheral phenolic hydroxyl groups. The product, cerium‑iron core-shell nanozyme, enabled effective stem cells labeling through endocytosis and exhibited catalase and superoxide dismutase activities within the cells. As a result, it could scavenge highly destructive hydroxyl radicals and peroxyl radicals, shielding stem cells from apoptosis in inflammatory environment and maintaining their differentiation ability. Additionally, when these functionalized stem cells were administered to mice with acute inflammation, not only did they alleviate disease symptoms, but they also allowed for the visualization using T2-weighted magnetic resonance imaging. This innovative therapeutic approach provides a new strategy for combatting diseases.

Enhancing the MRI contrast and hyperthermic properties of magnetic nanoflowers by modulating magnetisation dynamics using poly(butyl cyanoacrylate) shells: Towards multi-functional clinical carriers

Magnetic-polymeric complexes have strong potential as theranostic tools; when prepared as stable suspensions in the nano-range they are functionalisable carriers which can provide MRI (magnetic resonance imaging) tracking, static-field targeting and localised hyperthermia (on AC-field irradiation). In this work the effect of the polymer layer thickness on the MRI and hyperthermic efficacies, in clinically relevant ranges, for poly(butyl cyanoacrylate) encapsulated multi-domain γ-Fe2O3 nanoparticles was investigated for the first time. A series of nanocomposites were prepared at varying particle/polymer ratios revealing that progressively thicker polymer shells maximised the carrier potential and improved the MRI and hyperthermic efficacy due to enhancement of the Néel and partial suppression of the Brownian contribution to the dynamics of the magnetic moments. The implications for the development of multifunctional theranostic agents with optimised efficacy for AC-field triggered release are discussed.

Magnetic resonance imaging of mesenchymal stem cell – migration towards glioblastoma using a nano-calcium phosphate contrast agent

<img src=” https://s3.amazonaws.com/production.scholastica/article/94159/large/prnano_1162024ga.jpg?1708444945”> Tracking stem cell homing to the brain, their infiltration and brain tissue distribution, are critical for evaluating the efficacy of stem cell-based anti-glioma therapy. Here, we report the use of a biomineral magnetic nano-contrast agent, Fe-doped calcium phosphate nanoparticles (nCP:Fe), to label mesenchymal stem cells (MSCs) and track their migration towards brain tumor using magnetic resonance imaging (MRI). nCP:Fe labelled MSCs implanted intra-ventricularly in a rat C6-glioma model showed longitudinal migration towards tumor-region over 14 days, detected as hypointense signals in T2/T2* weighted-MR images, which was confirmed ex vivo using histological staining. Although, a small fraction of implanted MSCs migrated to the tumor-site, the study demonstrates that, MRI tracking of stem cells using nCP:Fe nano-contrast agent will facilitate better assessment of the efficacy of stem cell-guided anti-tumor therapy.

A multi-modality imaging strategy to determine the multiple in vivo fates of human umbilical cord mesenchymal stem cells at different periods of acute liver injury treatment.

Human umbilical cord mesenchymal stem cells (HUCMSCs) are applied for disease therapy as a new type of drug in many countries. Their effects are not only presented by live cells, but also apoptotic bodies or cell fragments of dead cells. Therefore, it is meaningful to determine the multiple fates of HUCMSCs in vivo. Although various probes combining different imaging modalities have been developed to label and trace transplanted HUCMSCs in vivo, the status of the cells (live, dead, or apoptotic) was not distinguished, and a thorough understanding of the multiple fates of HUCMSCs after transplantation in vivo is lacking. Therefore, a magnetic resonance (MR)/near infrared fluorescent (NIRF)/bioluminescence (BI) multi-modality imaging strategy was developed. Iron oxide nanoparticles (IONPs) were assembled into 100 nm nanoparticles using epigallocatechin gallate as a chemical linker to increase the MR signal and reduce the exocytosis of IONPs for direct cell labeling and longitudinal MR imaging tracking. Fluorescent probes for apoptosis (DEVD-Cy-OH) were also loaded in the above assemblies to monitor the cell status. Meanwhile, the cell surface was labeled with the fluorescent dye Cy7 via bioorthogonal reactions to visualize the NIRF signal. Luciferase was lentivirally transfected into live cells to generate bioluminescence. Such labeling did not affect either the viability, proliferation, migration, differentiation characteristics of HUCMSCs or their therapeutic effects on acute liver injury mice in vivo. The in vivo fates of HUCMSCs were monitored via MR/NIRF/BI multi-modality imaging in acute liver injury mice. Although MR and Cy7 signals aggregated in injured liver for 7 days, the BI signals persisted for less than 24 hours. There was an increase in DEVD-Cy-OH signals in the injured liver, but they were almost at the basal level. That means that HUCMSCs survive in mice for a short time, and the dead form of HUCMSCs accumulated in a large quantity and sustained for a long time, which might contribute to their therapeutic effect.

Mitral valve prolapse—arrhythmic faces of the valve disease

Mitral valve prolapse (MVP) is a relatively common mitral valvulopathy and the most common cause of isolated primary mitral regurgitation (MR) requiring surgical repair. It affects about 1–3% of the general population. Although MVP is viewed as a benign condition, the association between MVP and sudden cardiac death (SCD) has been proven. Patients with MVP have a three times higher risk of SCD than the general population. The underlying mechanisms and predictors of arrhythmias, which occur in patients with MVP, are still poorly understood. However, some echocardiographic features such as mitral annulus disjunction (MAD), bileaflet MVP (biMVP), and papillary muscle (PM) fibrosis were frequently linked with increased number of arrhythmic events and are referred to as “arrhythmogenic” or “malignant”. Arrhythmogenic MVP (AMVP) has also been associated with other factors such as female sex, polymorphic premature ventricular contraction (PVC), abnormalities of T-waves, and Pickelhaube sign on tissue Doppler tracing of the lateral part of the mitral annulus. Cardiac magnetic resonance (CMR) imaging and speckle tracking echocardiography are new tools showing significant potential for detection of malignant features of AMVP. This paper presents various data coming from electrocardiography (ECG) analysis, echocardiography, and other imaging techniques as well as compilation of the recent studies on the subject of MVP.

Cell Proliferation, Viability, Differentiation, and Apoptosis of Iron Oxide Labeled Stem Cells Transfected with Lipofectamine Assessed by MRI.

To assess in vitro and in vivo tracking of iron oxide labeled stem cells transfected by lipofectamine using magnetic resonance imaging (MRI), rat dental pulp stem cells (DPSCs) were characterized, labeled with iron oxide nanoparticles, and then transfected with lipofectamine to facilitate the internalization of these nanoparticles. Cell proliferation, viability, differentiation, and apoptosis were investigated. Prussian blue staining and MRI were used to trace transfected labeled cells. DPSCs were a morphologically spindle shape, adherent to culture plates, and positive for adipogenic and osteogenic inductions. They expressed CD73 and CD90 markers and lacked CD34 and CD45. Iron oxide labeling and transfection with lipofectamine in DPSCs had no toxic impact on viability, proliferation, and differentiation, and did not induce any apoptosis. In vitro and in vivo internalization of iron oxide nanoparticles within DPSCs were confirmed by Prussian blue staining and MRI tracking. Prussian blue staining and MRI tracking in the absence of any toxic effects on cell viability, proliferation, differentiation, and apoptosis were safe and accurate to track DPSCs labeled with iron oxide and transfected with lipofectamine. MRI can be a useful imaging modality when treatment outcome is targeted.

The impairment of intramural periarterial drainage in brain after subarachnoid hemorrhage

Interstitial fluid (ISF) from brain drains along the basement membranes of capillaries and arteries as Intramural Periarterial Drainage (IPAD); failure of IPAD results in cerebral amyloid angiopathy (CAA). In this study, we test the hypothesis that IPAD fails after subarachnoid haemorrhage (SAH). The rat SAH model was established using endovascular perforation method. Fluorescence dyes with various molecular weights were injected into cisterna magna of rats, and the pattern of IPAD after SAH was detected using immunofluorescence staining, two-photon fluorescent microscope, transmission electron microscope and magnetic resonance imaging tracking techniques. Our results showed that fluorescence dyes entered the brain along a periarterial compartment and were cleared from brain along the basement membranes of the capillaries, with different patterns based on individual molecular weights. After SAH, there was significant impairment in the IPAD system: marked expansion of perivascular spaces, and ISF clearance rate was significantly decreased, associated with the apoptosis of endothelial cells, activation of astrocytes, over-expression of matrix metalloproteinase 9 and loss of collagen type IV. In conclusion, experimental SAH leads to a failure of IPAD, clinically significant for long term complications such as CAA, following SAH.

Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy.

Labeling stem cells with magnetic nanoparticles is a promising technique for in vivo tracking and magnetic targeting of transplanted stem cells, which is critical for improving the therapeutic efficacy of cell therapy. However, conventional endocytic labeling with relatively poor labeling efficiency and a short labeling lifetime has hindered the implementation of these innovative enhancements in stem-cell-mediated regenerative medicine. Herein, we describe an advanced magnetothermal approach to label mesenchymal stem cells (MSCs) efficiently by local induction of heat-enhanced membrane permeability for magnetic resonance imaging (MRI) tracking and targeted therapy of stroke, where biocompatible γ-phase, ferrimagnetic vortex-domain iron oxide nanorings (γ-FVIOs) with superior magnetoresponsive properties were used as a tracer. This approach facilitates a safe and efficient labeling of γ-FVIOs as high as 150 pg of Fe per cell without affecting the MSCs proliferation and differentiation, which is 3.44-fold higher than that by endocytosis labeling. Such a high labeling efficiency not only enables the ultrasensitive magnetic resonance imaging (MRI) detection of sub-10 cells and long-term tracking of transplanted MSCs over 10 weeks but also endows transplanted MSCs with a magnetic manipulation ability in vivo. A proof-of-concept study using a rat stroke model showed that the labeled MSCs facilitated MRI tracking and magnetic targeting for efficient replacement therapy with a significantly reduced dosage of 5 × 104 transplanted cells. The findings in this study have demonstrated the great potential of the magnetothermal approach as an efficient labeling technique for future clinical usage.

Multifunctional surface functionalized magnetic iron oxide nanoparticles for biomedical applications: A review

Magnetic iron oxide nanoparticle-based multifunctional platforms have been explored extensively in biomedical applications. Modifications and integrations of IONPs with different entities viz. organic polymer, doping with inorganic materials, loading with drug, fluorescent dye, or antibodies make them appropriate for their application in broad spectrum of biomedical fields. This review presents and summarizes the fabrication strategies of multifunctional magnetic nanoparticles based on the modification and surface functionalization of MNP. Multifunctional IONPs based recent advances covering a wide array of applications like biosensing and pathogen detection, magnetic resonance imaging (MRI) and biomarker tracking, magnetofection and gene therapy, hyperthermia and chemotherapy, drug delivery and targeted cell killing, bioimaging and therapeutics, stem cell detection and therapy, tissue engineering and organ transplant, nano-vaccines and immune system activation, microbe targeting and destruction, and COVID19 management are also covered.

A window into eye movement dysfunction following mTBI: A scoping review of magnetic resonance imaging and eye tracking findings.

Mild traumatic brain injury (mTBI), commonly known as concussion, is a complex neurobehavioral phenomenon affecting six in 1000 people globally each year. Symptoms last between days and years as microstructural damage to axons and neurometabolic changes result in brain network disruption. There is no clinically available objective biomarker to diagnose the severity of injury or monitor recovery. However, emerging evidence suggests eye movement dysfunction (e.g., saccades and smooth pursuits) in patients with mTBI. Patients with a higher symptom burden and prolonged recovery time following injury may show higher degrees of eye movement dysfunction. Likewise, recent advances in magnetic resonance imaging (MRI) have revealed both white matter tract damage and functional network alterations in mTBI patients, which involve areas responsible for the ocular motor control. This scoping review is presented in three sections: Section 1 explores the anatomical control of eye movements to aid the reader with interpreting the discussion in subsequent sections. Section 2 examines the relationship between abnormal MRI findings and eye tracking after mTBI based on the available evidence. Finally, Section 3 communicates gaps in our knowledge about MRI and eye tracking, which should be addressed in order to substantiate this emerging field.

Extracellular magnetic labeling of biomimetic hydrogel-induced human mesenchymal stem cell spheroids with ferumoxytol for MRI tracking.

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.

Ferromagnetic Vortex Iron Oxide Nanorings Modified with Integrin β1 Antibody for Targeted MRI Tracking of Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have demonstrated great potential for tissue engineering and regenerative medicine applications. Noninvasive and real-term tracking of transplanted MSCs in vivo is crucial for studying the distribution and migration of MSCs, and their role in tissue injury repair. This study reports on the use of ferrimagnetic vortex iron oxide (FVIO) nanorings modified with anti-human integrin β1 for specific recognition and magnetic resonance imaging (MRI) tracking of human MSCs (hMSCs). Integrin β1 is highly expressed at all stem cell proliferation and differentiation stages. Therefore, the anti-integrin β1 antibody (Ab) introduced in FVIO targets integrin β1, thus enabling FVIO to target stem cells at any stage. This is unlike the traditional MRI-based monitoring of transplanted stem cells, which usually requires pre-labeling the stem cells with tracers before injection. Because of the ability to recognize hMSCs, the Ab-modified FVIO nanotracers (FVIO-Ab) have the advantage of not requiring pre-labeling before stem cell transplantation. Furthermore, the FVIO-Ab nanotracers have high T*₂ contrast resulting from the unique magnetic properties of FVIO which can improve the MRI tracking efficiency of stem cells. This work may provide a new way for stem cell labeling and in vivo MRI tracking, thus reducing the risks associated with stem cell transplantation and promoting clinical translation.

Validation of the New Pediatric Pulmonary Hypertension Risk Score by Cardiac Magnetic Resonance Imaging and Speckle Tracking Echocardiography. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN)

<h3>Purpose</h3> The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) developed in 2019 a pediatric pulmonary hypertension (PH) risk score to assess the risk and severity of PH in children and young adults. This prospective observational study seeks to validate the EPPVDN pediatric PH risk score by correlations with suitable and independent variables from cardiac magnetic resonance imaging (CMR) and speckle tracking echocardiography. <h3>Methods</h3> Twenty children with PAH were enrolled into the study (age: 10.8±1.0, range 4.0- 17.6 years). During the same inpatient stay the invasive and non-invasive EPPVDN pediatric PH risk scores were determined and a protocol-driven CMR study was performed. Subsequently, we correlated the risk scores with conventional and strain CMR variables and advanced echocardiographic variables, including strain analysis (speckle-tracking). In addition, we applied the risk score to 9 children with PAH who received add-on selexipag therapy. Before and approximately 6 months after selexipag start the risk score and echocardiographic RV strain were determined and delta-changes of both were correlated. <h3>Results</h3> We observed significant (p<0.001) and strong correlations of conventional CMR (r=0.69-0.88), CMR strain (r=0.71-0.88), advanced echocardiographic (r=0.65-0.88) and echocardiographic strain variables (r=0.67-0.86), with the EPPVDN PHrisk score. The EPPVDN higher risk scores correlated stronger with the CMR-, ECHO-, and CMR-strain variables, when compared to the lower risk scores. In the add-on selexipag cohort, the change in ECHO-derived RV strain correlated most strongly and significantly with the change in the invasive higher risk score (r= -0.72, p<0.004). <h3>Conclusion</h3> We found strong correlations of conventional, outcome-relevant CMR and strain variables (CMR, ECHO) with the EPPVDN pediatric PH risk scores, and thus validated the score via independent methods. The novel EPPVDN pediatric PH risk score will be very useful in routine clinical care, and can now be applied in larger prospective, pharma-interventional PAH studies in children and young adults. According open access online tools for rapid, comprehensive risk assement are in preparation.

Altered White Matter and microRNA Expression in a Murine Model Related to Williams Syndrome Suggests That miR-34b/c Affects Brain Development via Ptpru and Dcx Modulation.

Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by a de novo hemizygous deletion of ~26 genes from chromosome 7q11.23, among them the general transcription factor II-I (GTF2I). By studying a novel murine model for the hypersociability phenotype associated with WS, we previously revealed surprising aberrations in myelination and cell differentiation properties in the cortices of mutant mice compared to controls. These mutant mice had selective deletion of Gtf2i in the excitatory neurons of the forebrain. Here, we applied diffusion magnetic resonance imaging and fiber tracking, which showed a reduction in the number of streamlines in limbic outputs such as the fimbria/fornix fibers and the stria terminalis, as well as the corpus callosum of these mutant mice compared to controls. Furthermore, we utilized next-generation sequencing (NGS) analysis of cortical small RNAs’ expression (RNA-Seq) levels to identify altered expression of microRNAs (miRNAs), including two from the miR-34 cluster, known to be involved in prominent processes in the developing nervous system. Luciferase reporter assay confirmed the direct binding of miR-34c-5p to the 3’UTR of PTPRU—a gene involved in neural development that was elevated in the cortices of mutant mice relative to controls. Moreover, we found an age-dependent variation in the expression levels of doublecortin (Dcx)—a verified miR-34 target. Thus, we demonstrate the substantial effect a single gene deletion can exert on miRNA regulation and brain structure, and advance our understanding and, hopefully, treatment of WS.

MRI tracking of human Wharton's jelly stem cells seeded onto acellular dermal matrix labeled with superparamagnetic iron oxide nanoparticles in burn wounds.

In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies. This study investigated tracking of human Wharton's jelly stem cells (hWJSCs) seeded onto an acellular dermal matrix (ADM) and labeled with superparamagnetic iron oxide nanoparticles (SPIONs) by magnetic resonance imaging (MRI) in burn injury. The hWJSCs were characterized and assessed for growth kinetics. A total of 30 rats were enrolled in three equal groups. Group 1 underwent scald burn injury left without treatment, the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM. Tensile strength was evaluated before and after interventions, real time PCR assessed apoptosis, and Prussian blue staining, scanning electron microscopy (SEM) and MRI were used for the tracking of labeled cells. The hWJSCs exhibited mesenchymal stem cell properties. Population doubling time was 40.1 hours. SPIONs did not show any toxic effect. The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression. Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining, SEM and MRI until day 21. There was a significant difference between the Young's moduli of normal skin and the group receiving hWJSCs seeded onto an ADM. Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo. This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

Use of Magnetic Resonance Imaging to Assess the Regenerative Effects of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rabbit Cartilaginous Laryngeal Defect Model

BackgroundStenosis and scar formation after repair of laryngeal tissue defects are serious problems that can significantly influence a patient's quality of life.ObjectiveIn this study, we evaluated the use of magnetic resonance imaging to assess the efficacy of adipose tissue-derived mesenchymal stem cells (ASCs) on cartilaginous regeneration in an experimental rabbit model.MethodsTen male white Dutch rabbits each had a 5 mm cartilaginous defect created surgically in the right and left thyroid lamina. On the right side, ASCs labeled with iron oxide particles were infused. As a control, the left side was left untreated. Repair of the defects were then evaluated by direct observation, histological evaluation, and magnetic resonance imaging monitoring done on days 1, 7, 14, and 28.ResultsHistological examination revealed that compared with control, transplanted ASCs significantly increased cartilage regeneration (P ˂ 0.001), reduced inflammation (P ˂ 0.001), and fibrosis (P = 0.050). Magnetic resonance imaging tracking showed accurate placement and viability of the infused ASCs, as evidenced by low signal intensity onT2 weighted images at the level of the right thyroid cartilage.ConclusionsInfusion of ASCs improved laryngeal regeneration of surgically induced cartilaginous defects while decreasing fibrous tissue formation in this in vivo rabbit model. Furthermore, magnetic resonance imaging was shown to be a useful, noninvasive method to track correct ASCs placement and viability in cartilage regeneration in this animal model.