Nanomagneto-assisted cell- and gene therapy in the heart for the treatment of post-infarct complications

• Antragsteller: Privatdozent Dr. Wilhelm Röll
• Fachliche Zuordnung: Pharmakologie
• Förderung: Förderung von 2009 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 40403621

Myocardial pump failure and tachycardic ventricular post-infarct arrhythmias represent the two major and potentially lethal complications after myocardial infarction. We plan to further develop novel site-specific treatment regimen against these complications using magnetic nanoparticles (MNP) assisted cardiac cell and/or gene therapy in mouse. We found that the combined use of MNP and magnets strongly enhances engraftment rates of progenitor cells. We will explore the underlying mechanism(s) and based on these insights design strategies to further improve the functional integration of grafted cells. Besides these measures, we also plan to reduce the size of the post-infarct scar formation and pathological left ventricular remodelling via overexpression of anti-apoptotic and/or pro-angiogenic genes/factors within the infarct and the border zone. Similar strategies are also tested by grafting cells overexpressing one or several of these factors. Our goal is the systemic delivery of genes and/or cells and we will explore the feasibility of this approach employing MNP-loaded cells or Lentivirus (LV)/MNP complexes in the murine hindlimb model. In addition, the occurrence of tachycardic ventricular arrhythmias post-infarct will be treated with LV/MNP-based Cx43 overexpression within the scar. All this experimental work is aimed at improving the long-term outcome post-myocardial infarction and at reducing the accompanying most frequent complications.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 917: Targeting von Gen- und Zellbasierten Therapien mittels Magnetischer Nanopartikel
• Beteiligte Person: Professor Dr. Bernd Fleischmann