Project Details
Projekt
Nanomagneto-assisted cell- and gene therapy in the heart for the treatment of post-infarct complications
Applicant
Privatdozent Dr. Wilhelm Röll
Subject Area
Pharmacology
Term
from 2009 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme
Research Units
Participating Person
Professor Dr. Bernd Fleischmann
