Clin Res Cardiol 100, Suppl 1, April 2011

P650 - Electrical Integration of Transplanted Cardiomyocytes Derived from Induced Pluripotent Stem Cells
G. Peinkofer1, M. Halbach1, S. Baumgartner1, B. Krausgrill2, A. Fatima3, T. Saric3, J. Hescheler3, J. Müller-Ehmsen2
1Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln, Köln; 2Klinik III f. Innere Med., Labor f. Herzmuskelphys. und Mol. Kardiologie, Klinikum der Universität zu Köln, Köln; 3Institut für Neurophysiologie, Klinikum der Universität zu Köln, Köln;
Objective: Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded as most promising cell type for cardiac cell replacement therapy. A functional integration of these cells is crucial for efficiency and safety, but has not been demonstrated, yet. Thus, we investigated the electrical integration of transplanted iPSCM into host tissue.
Methods: Genetically modified murine iPSCM, expressing eGFP and a puromycin resistance under control of the alpha-MHC promoter, were purified by antibiotic selection. Purified iPSCM were injected into adult mouse hearts (2 injections, 500,000 cells per site). At different times after transplantation (2-8 days), recipients were sacrificed and viable ventricular tissue slices (thickness: 150 µm) were prepared. Slices were focally stimulated by a unipolar electrode placed in host tissue. Recordings of action potentials were performed by glass microelectrodes in transplanted iPSCM, which could be identified by their green fluorescence, and in host cardiomyocytes within the tissue slices.
Results: Electrophysiological properties of transplanted iPSCM differed significantly from those of host cardiomyocytes (P<0.05 for all parameters). IPSCM had a lower maximum diastolic potential (-50.1±5.6 mV vs. -70.9±5.1 mV), amplitude (49.7±3.4 mV vs. 75.0±11.5 mV) and maximum upstroke velocity (11.1±1.3 V/s vs. 102.2±31.7 V/s). APD50 was longer (21.7±10.1 ms vs. 13.8±10.0 ms), APD90 was shorter (37.2±15.4 ms vs. 95.7±20.2 ms). Coupling of iPSCM to host tissue could be clearly demonstrated in some transplanted iPSCM showing no conduction blocks even at high stimulation frequencies of up to 8 Hz, while others had blocks at lower stimulation frequencies or were not electrically integrated at all.
Conclusions: IPSCM are able to integrate electrically into host tissue, but conduction blocks are frequent. Action potential properties of transplanted iPSCM differ considerably from those of recipient cardiomyocytes.
Clin Res Cardiol 100, Suppl 1, April 2011
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-011-1100-y