Dara L. Kraitchman

Bio: Dara L. Kraitchman is an academic researcher from Johns Hopkins University School of Medicine. The author has contributed to research in topics: Stem cell & Magnetic resonance imaging. The author has an hindex of 38, co-authored 150 publications receiving 8090 citations. Previous affiliations of Dara L. Kraitchman include Johns Hopkins University & University of Pennsylvania.

Iron oxide MR contrast agents for molecular and cellular imaging.

Abstract: Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2(*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the ‘proof-of-principle’ type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors. Copyright © 2004 John Wiley & Sons, Ltd.

In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction

Abstract: Background— We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods and Results— Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16×107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals. Conclusion— MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.

Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Abstract: Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of...

Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis.

Abstract: Magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIO)-labeled cells is a relatively new technique to non-invasively determine the biodistribution and migration of transplanted stem cells. A number of studies have recently reported encouraging results in the use of bone marrow-derived mesenchymal stem cells (MSCs) for repair of a variety of tissues. For MR tracking of SPIO-labeled MSCs, it is important to determine the effect that the magnetic labeling procedure may have on the differentiation capacity of labeled MSCs. Human MSCs were labeled with poly-L-lysine (PLL)-coated Feridex, with Feridex being an FDA-approved SPIO formulation in an off-label application, and assayed for cellular differentiation using five different assays. As compared with unlabeled controls, labeled MSCs exhibited an unaltered viability, proliferated similarly, and underwent normal adipogenic and osteogenic differentiation. However, there was a marked inhibition of chondrogenesis. The blocking of chondrogenic activity was mediated by the Feridex, rather than by the transfection agent (PLL). This is the first report showing Feridex blocking of cellular differentiation down a specific pathway (while not affecting viability and proliferation), and caution should thus be exercised when using Feridex-labeled MSCs for chondrogenic MR tracking studies. On the other hand, no detrimental effects of Feridex-labeling are anticipated for MR-guided osteogenic or adipogenic transplantation studies.

Applications of magnetic nanoparticles in biomedicine

Abstract: The physical principles underlying some current biomedical applications of magnetic nanoparticles are reviewed. Starting from well-known basic concepts, and drawing on examples from biology and biomedicine, the relevant physics of magnetic materials and their responses to applied magnetic fields are surveyed. The way these properties are controlled and used is illustrated with reference to (i) magnetic separation of labelled cells and other biological entities; (ii) therapeutic drug, gene and radionuclide delivery; (iii) radio frequency methods for the catabolism of tumours via hyperthermia; and (iv) contrast enhancement agents for magnetic resonance imaging applications. Future prospects are also discussed.

Cytotoxicity of Nanoparticles

Abstract: Human exposure to nanoparticles is inevitable as nanoparticles become more widely used and, as a result, nanotoxicology research is now gaining attention. However, while the number of nanoparticle types and applications continues to increase, studies to characterize their effects after exposure and to address their potential toxicity are few in comparison. In the medical field in particular, nanoparticles are being utilized in diagnostic and therapeutic tools to better understand, detect, and treat human diseases. Exposure to nanoparticles for medical purposes involves intentional contact or administration; therefore, understanding the properties of nanoparticles and their effect on the body is crucial before clinical use can occur. This Review presents a summary of the in vitro cytotoxicity data currently available on three classes of nanoparticles. With each of these nanoparticles, different data has been published about their cytotoxicity due to varying experimental conditions as well as differing nanoparticle physiochemical properties. For nanoparticles to move into the clinical arena, it is important that nanotoxicology research uncovers and understands how these multiple factors influence the toxicity of nanoparticles so that their undesirable properties can be avoided.