cyanine-dye-3 and Myocardial-Infarction

Nucleic acid (NA)-based therapy is proposed to address serious diseases such as cardiovascular diseases (CVDs). Powerful NA delivery vehicles are essential for effective gene therapy. Herein, a novel type of delivery vehicle, an unlockable core-shell nanocomplex (Hep@PGEA) with self-accelerating NA release, is structurally designed. Hep@PGEA is composed of disulfide-bridged heparin nanoparticle (HepNP) core and low-toxicity PGEA cationic shell. In comparison with NA, heparin, a negatively charged polysaccharide macromolecule, exhibits stronger interactions with cationic species. Upon the breakdown of redox-responsive HepNP cores, unlocked heparin would interact with the outer cationic shells and replace the condensed NA to facilitate NA release. Such unique Hep@PGEA is successfully explored for effective miRNA-pDNA staged gene therapy of myocardial infarction (MI), one of the most serious CVDs. With the progression of MI, glutathione amounts in heart tissues increase. MiR-499 (for the inhibition of cardiomyocyte apoptosis) and plasmid encoding vascular endothelial growth factor (for the promotion of angiogenesis) are sequentially delivered for systemic treatment of MI. Such treatment produces impressive results in restoring heart function and suppressing cardiac hypertrophy. Due to the wide existence of redox agents in cells, the proposed unlockable delivery nanovehicle and staged therapy strategy can provide new methods to effectively treat different serious diseases.

Topics: Animals; Carbocyanines; DNA; Genetic Therapy; Glutathione; Heparin; Mice; MicroRNAs; Microscopy, Atomic Force; Microscopy, Confocal; Myocardial Infarction; Nanoparticles; Particle Size; Polymethacrylic Acids; Vascular Endothelial Growth Factor A

The aim of the current study is to test the ability to label and detect murine embryonic stem cell-derived cardiovascular progenitor cells (ES-CPC) with cardiac magnetic resonance (CMR) using the novel contrast agent Gadofluorine M-Cy3 (GdFM-Cy3).. Cell therapy shows great promise for the treatment of cardiovascular disease. An important limitation to previous clinical studies is the inability to accurately identify transplanted cells. GdFM-Cy3 is a lipophilic paramagnetic contrast agent that contains a perfluorinated side chain and an amphiphilic character that allows for micelle formation in an aqueous solution. Previous studies reported that it is easily taken up and stored within the cytosol of mesenchymal stem cells, thereby allowing for paramagnetic cell labeling. Investigators in our laboratory have recently developed techniques for the robust generation of ES-CPC. We reasoned that GdFM-Cy3 would be a promising agent for the in vivo detection of these cells after cardiac cell transplantation.. ES-CPC were labeled with GdFM-Cy3 by incubation. In vitro studies were performed to assess the impact of GdFM-Cy3 on cell function and survival. A total of 500,000 GdFM-Cy3-labeled ES-CPC or control ES-CPC were injected into the myocardium of mice with and without myocardial infarction. Mice were imaged (9.4-T) before and over a 2-week time interval after stem cell transplantation. Mice were then euthanized, and their hearts were sectioned for fluorescence microscopy.. In vitro studies demonstrated that GdFM-Cy3 was easily transfectable, nontoxic, stayed within cells after labeling, and could be visualized using CMR and fluorescence microscopy. In vivo studies confirmed the efficacy of the agent for the detection of cells transplanted into the hearts of mice after myocardial infarction. A correspondence between CMR and histology was observed.. The results of the current study suggest that it is possible to identify and potentially track GdFM-Cy3-labeled ES-CPC in murine infarct models via CMR.

Topics: Animals; Carbocyanines; Cell Line; Cell Proliferation; Cell Survival; Contrast Media; Disease Models, Animal; Embryonic Stem Cells; Female; Fluorescent Dyes; Fluorocarbons; Magnetic Resonance Imaging; Mesenchymal Stem Cell Transplantation; Mice; Mice, SCID; Microscopy, Fluorescence; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Organometallic Compounds; Staining and Labeling; Time Factors

Topics: Animals; Carbocyanines; Cell Proliferation; Cell Survival; Contrast Media; Fluorescent Dyes; Fluorocarbons; Humans; Magnetic Resonance Imaging; Mice; Microscopy, Fluorescence; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Organometallic Compounds; Staining and Labeling; Stem Cell Transplantation; Stem Cells; Time Factors