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The overall goal of our research is to develop noninvasive magnetic resonance (MR) imaging and optical imaging (OI) methods, using iron oxide nanoparticles and fluorescent dyes, for a non-invasive and repetitive depiction of human embryonic stem cells (hESCs). Our previous studies have shown, that FDA approved MR contrast media can be used to target adult stem cells, and that these contrast agent labeled stem cells can be visualized non-invasively with MR imaging. However, it has been also shown, that these contrast media may impair the viability and differentiation capacity of labeled stem cells, if internalized into the cells in too high quantities. Specific cell types, such as embryonic stem cells, have been shown to be particularly susceptible to such effects of MR contrast agents. The overall hypothesis is that our cell labeling and imaging techniques can be applied, tailored and optimized for a sensitive depiction of hESCs without any impairment of their viability, function and differentiation capacity. In addition, our planned studies should elucidate the long term MR and OI signal characteristics of iron oxide nanoparticle labeled hESCs. Complementary immunohistochemistry and fluorescence microscopy studies as well as spectrometry measurements will give further insight into biological and physicochemical changes underlying the observed signal intensity changes of the labeled cells on imaging studies. The cell labeling and imaging method should facilitate investigations of hESC based therapies in experimental models, and may ultimately help to assess clinical responses to hESC based therapies in patients. Daldrup-Link HE, Rudelius M, Oostendorp RAJ, Settles M, Piontek G, Metz S, Heinzmann U, Rummeny EJ, Schlegel J, Link TM: Targeting of Hematopoietic Progenitor Cells with MR Contrast Agents. Radiology 228: 760-767, 2003 Daldrup-Link HE, Rudelius M, Metz S, Piontek G, Settles M, Pichler B, Heinzmann U, Weinmann HJ, Schlegel J, Link TM, Rummeny EJ, Oostendorp RAJ: Stem cell tracking with Gadophrin-2 a bifunctional contrast agent for MR imaging, optical imaging and fluorescence microscopy. Eur J Nucl Med Mol Imaging 31(9):1312-21, 2004. Daldrup-Link HE, Rudelius M, Piontek G, Metz S, Bräuer R, Debus G, Corot C, Schlegel J, Link TM, Peschel C, Rummeny EJ, Oostendorp RAJ: Migration of iron oxide labeled human hematopoietic progenitor cells in a xenotransplant model: in vivo monitoring using clinical magnetic resonance imaging equipment. Radiology 234(1): 197-205, 2005 Daldrup-Link HE, Meier R, Rudelius M, Piontek G, Piert M, Metz S, Settles S, Uherek C, Schlegel J, Rummeny EJ: In-vivo Tracking of genetically engineered anti-HER2/neu directed Natural Killer to HER2/neu positive Mammary Tumors with Magnetic Resonance Imaging. Eur Radiol 15(1): 4-13, 2005 Henning T, Saborowski O, Golovko D, Boddington S, Bauer J, Fy Y, Meier R, Pietsch H, Sennino B, Daldrup-Link HE: Cell labeling with the positive MR contrast agent Gadofluorine M. Eur Radiol 17(5):1226-34, 2007 |
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