Abstract 16620: Electrical Integration of Transplanted Cardiomyocytes Derived from Induced Pluripotent Stem Cells
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.
- © 2010 by American Heart Association, Inc.