Journal
PLOS ONE
Volume 7, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0039490
Keywords
-
Categories
Funding
- German Federal Ministry of Education and Research, BioChancePlus program [0313191]
- German Helmholtz Association, Mecklenburg-Vorpommern, German Federal Ministry of Education and Research, German Research Foundation (Nachwuchsgruppe Regenerative Medizin Regulation der Stammzellmigration) [0402710]
- Forderkennzeichen (Ministry of Education (Germany, Berlin) [0312138 A]
- Ministry of Economy (Mecklenburg-West Pommerania, Schwerin) [V220-630-08-TFMV-F/S-035]
- Marie Curie International Research Staff Exchange Scheme (IRSES, FP7-PEOPLE-IRSES
- Reference and Translation Center for Cardiac Stem Cell Therapy
- [Sonderforschungsbereich/Transregio 37]
- [B5]
- [B2]
- [A4]
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This study assessed the concept of whether delivery of magnetic nanobeads (MNBs)/adenoviral vectors (Ad)-encoded hVEGF gene (Ad(hVEGF)) could regenerate ischaemically damaged hearts in a rat acute myocardial infarction model under the control of an external magnetic field. Adenoviral vectors were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transduction efficacy of MNBs/Ad-encoded luciferase gene (Ad(luc)) was compared with Ad(luc) alone in human umbilical vein endothelial cells (HUVECs) under magnetic field stimulation. In vivo, in a rat acute myocardial infarction (AMI) model, MNBs/Ad(hVEGF) complexes were injected intravenously and an epicardial magnet was employed to attract the circulating MNBs/Ad(hVEGF) complexes. In vitro, compared with Ad(luc) alone, MNBs/Ad(luc) complexes had a 50-fold higher transduction efficiency under the magnetic field. In vivo, epicardial magnet effectively attracted MNBs/Ad(hVEGF) complexes and resulted in strong therapeutic gene expression in the ischemic zone of the infarcted heart. When compared to other MI-treated groups, the MI-M+/Ad(hVEGF) group significantly improved left ventricular function (p<0.05) assessed by pressure-volume loops after 4 weeks. Also the MI-M+/Ad(hVEGF) group exhibited higher capillary and arteriole density and lower collagen deposition than other MI-treated groups (p<0.05). Magnetic targeting enhances transduction efficiency and improves heart function. This novel method to improve gene therapy outcomes in AMI treatment offers the potential into clinical applications.
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