succimer and Ischemia

Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.

Topics: Adipose Tissue; Animals; Cell Death; Cell Differentiation; Cell Survival; Disease Models, Animal; Ferric Compounds; Ferrocyanides; Flow Cytometry; Fluorescent Antibody Technique; Green Fluorescent Proteins; Hindlimb; Hydrodynamics; Immunohistochemistry; Ischemia; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Multipotent Stem Cells; Nanoparticles; Particle Size; Staining and Labeling; Stem Cell Transplantation; Stem Cells; Succimer

An abnormal filtration fraction or a significant divergence between a kidney's ability to extract Tc-99m dimercaptosuccinic acid (DMSA) and other function parameters, such as the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF), could lead to different estimates of relative or absolute renal function, depending on the radiopharmaceutical administered. To evaluate this possible divergence, we measured the relative GFR (I-125 iothalamate), ERPF (I-131 hippurate), and Tc-99m DMSA accumulation in adult male Sprague-Dawley rats with unilateral ureteral obstruction or unilateral ischemia at various times after renal injury. The relative ERPF of the obstructed kidney was significantly greater than the relative GFR at all time periods studied; significant but less dramatic differences were noted comparing DMSA with GFR in obstruction and DMSA and ERPF with GFR in ischemia. In evaluating renal disease, it is important to consider the functional parameter reflected by the administered radiopharmaceutical as well as the underlying disease state.

Topics: Animals; Glomerular Filtration Rate; Hippurates; Iodine Radioisotopes; Iothalamic Acid; Ischemia; Kidney; Kidney Diseases; Male; Radioisotope Renography; Rats; Rats, Inbred Strains; Regional Blood Flow; Succimer; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Ureteral Obstruction

The effect of transient renal ischemia on renal concentration and distribution of 99mTc-HEDP, 99mTc-DMSA, and 99mTc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. 99mTc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1--4 hours after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. 99mTc-HEDP may be useful in evaluation of renal failure secondary to tubular injury.

Topics: Acute Kidney Injury; Animals; Calcium; Etidronic Acid; Female; Ischemia; Kidney; Kidney Tubular Necrosis, Acute; Male; Rabbits; Radionuclide Imaging; Succimer; Technetium