Intramyocardial transplantation of bioartificial iPS-myocardial-splints for restauration of ischemic myocardium in a rat model. In vivo evaluation of survival and impact of transplated tissue on left ventricular function

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Recent findings demonstrate that intramyocardial application of stem cell (derivates) do not significantly restore damaged myocardium due to limited cell survival and adverse biodistribution. The transplantation of solid bioartificial myocardial tissue (bioartificial cardiac tissue, BCT) results in better outcome. However, currently the clinical application of BCTs with adequate size and vascular supply seem to be far away. As an alternative conception we would favour the application of multiple of small BCT-splints (size: 6 mm x 1 mm2). These BCT-splints can potentionally neovascularize and couple functionally to the recipient´s myocardium.The new intramyocardial implantation technique should be primarily established using syngenic BCT-splints based on neonatal cardiomyocytes and compared functionally and histologically with standardized epicardially implantated BCT-splints. Afterwards, these findings should be transferred to BCT-splints which are generated from induced pluripotent stem cells of mice (miPS). The miPS-BCT-splints will be implanted in a chronic ischemic myocardium of nude rats. The miPS-BCTs are transgenic for luciferase, thus the in vivo survival of these miPS-BCTs will be evaluated for 28 days using Luciferase Bioimaging. Functional analyses will be performed by echocardiography, magnetic resonance tomography and conductance catheter. The goal of this project is to evaluate whether intramyocardially implanted BCT-splints functionally integrate in recpipients myocardium and consequently improve the left ventricular pump function. Considering recent progresses in stem cell research, this method would introduce new perspectives for the clinical application of iPS cell based restauration of ischemic myocardium.