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Background Transplantation of mononuclear cells (MNCs) has previously been tested as

Background Transplantation of mononuclear cells (MNCs) has previously been tested as a method to induce therapeutic angiogenesis to treat limb ischemia in clinical trials. (as a marker of capillary endothelial cells) in the intact Mn-MNCs implanted site at 43 Sitagliptin phosphate manufacturer days was significantly larger than that at a site implanted with dead Mn-MNCs. Conclusions Rabbit Polyclonal to SH2B2 The present Mn-enhanced MRI method enabled visualization of the transplanted area with a 150C175 m in-plane spatial resolution and allowed the migration of labeled-MNCs to be observed for long periods in the same subject. After further optimization, MRI-based Mn-enhanced cell-tracking could be a useful technique for evaluation of Sitagliptin phosphate manufacturer cell therapy both in research and clinical applications. Introduction Cell therapy to treat cardiovascular disease has come of age. For instance, bone marrow-derived mononuclear cells (MNCs) have been used for therapeutic neovascularization not only in animal models[1], [2], [3], [4], but also in the clinical setting[5], [6]. Peripheral blood MNCs have also been used to induce therapeutic neovascularization for critical limb ischemia[7], [8] and myocardial infarction[9], [10]. However, methods that can be used to reliably evaluate therapeutic effects and migration of transplanted MNCs are not well established. monitoring of the healing process after cell transplantation, particularly the fate of transplanted cells, is required for high-precision optimization in order to improve the efficacy of such cell therapies. In addition, non-invasive imaging of transplanted MNCs may contribute to understanding the mechanism underlying therapeutic effects such as angiogenesis[11]. There is a rapidly growing interest in tracking cell movements both in animals and humans[12], [13]. Tracking MNCs with magnetic resonance imaging (MRI) has been used in living tissues such as skeletal muscle, heart and brain to visualize both the regenerative therapeutic effect and the location of migrated cells with a high spatial resolution[14], [15], [16]. Iron oxide nanoparticles can enhance cell visualization because the susceptibility difference significantly alters T2*, especially in high field MRI[17]. Dextran-coated iron oxide nanoparticles have been found to Sitagliptin phosphate manufacturer have a wide clinical application for detection of hepatic tumors[18]. On the other hand, iron oxide particles still have several shortcomings as cell-labeling agents. First, the iron oxide particles stay inside cells for long periods[19], become engulfed by cardiac macrophages[20], and do Sitagliptin phosphate manufacturer not indicate cell viability. Second, iron oxide particles often provide negative contrast that is difficult to distinguish from dark regions in the body, such as air cavities, veins and other regions where there is intrinsic iron deposition after injury. Third, iron oxide particles need specialized materials and methods for cell labeling such as vectors, [21] transfection reagents[22] and electroporation[23]. Manganese (Mn) is known to be a toxic substance that causes manganism through chronic exposure in environments such as mines[24]. The divalent manganese ion (Mn2+) is also known to be essential for living organisms. For this reason, there has been a recent renewed interest in Mn2+ as a potentially useful positive contrast agent for T1 weighted MRI. The kinetics of Mn2+ in the cell mimics the kinetics of calcium ions (Ca2+) in many biological systems[25], [26], as Mn2+ is known to enter cells through ligand- or voltage-gated Ca2+ channels[27]. Recently, Mn2+ agents have found application with manganese-enhanced MRI (MEMRI) for visualization of many biological features, including neuronal pathways[28] and neuro/cytoarchitecture[29], [30]. Previous work has used the fact that Mn2+ can enter cells via voltage gated Ca2+ channels during stimulation in order to enhance excitable cells in the brain[31], [32], and.