Correction: optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

Abstract Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.</p

Intravenous human umbilical cord-derived mesenchymal stromal cell administration in models of moderate and severe intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggests mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared to other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary

Removal of the cortical projections alters expression of NOS in the different cell types of the superficial layers of the superior colliculus in rats

Nitric oxide has several biological roles and nitric oxide synthase (NOS) is expressed in the nervous system, and co-localizes with NADPH-diaphorase. The superficial layers of the superior colliculus (SC), which receive retinal and cortical inputs, present NADPH-d staining in a sub-population of neurons that include all cell types. We have previously shown, by NADPH-diaphorase, that eye enucleation alters the intracellular distribution of NOS. Here, we studied the effect of cortical ablation on NOS expression by neurons in collicular superficial layers. Our results show that cortical ablation alters the proportion of different NOS-positive cell types, but not the intracellular distribution of the enzyme.O óxido nítrico apresenta diversos papéis biológicos e a óxido nítrico sintase (ONS) é expressa no sistema nervoso, co-localizando-se com a NADPH-diaforase. As camadas superficiais do colículo superior (CS), as quais recebem aferências retinianas e corticais, possuem marcação para NADPH-diaforase numa sub-população de neurônios que inclui todos os tipos celulares. Previamente demostramos, por NADPH-diaforase, que a enucleação ocular altera a distribuição intracelular da ONS. Neste trabalho estudamos o efeito da ablação cortical na expressão da ONS por neurônios das camadas superficiais coliculares. Nossos resultados demonstraram que a ablação cortical altera as proporções dos diferentes tipos celulares ONS positivos mas não a distribuição intracelular da ONS

Development and Application of Nanoparticles in Biomedical Imaging

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