Abstract 9917: Electrical Coupling and Action Potential Properties of Transplanted Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Comparison with Fetal Cardiomyocytes

Abstract

A functional integration and maturation of transplanted cardiomyocytes prevents arrhythmias and enhances synergistic contractions of transplanted and host tissue. We compared electrical coupling and action potential (AP) properties of transplanted induced pluripotent stem cell-derived cardiomyocytes (iPSCM), which are regarded as promising cell type for cell therapy, and fetal cardiomyocytes (FCM). Methods: Murine iPSCM expressing eGFP and a puromycin resistance under control of the α-MHC promoter, were purified by antibiotic selection and dissociated at day 16 of differentiation. FCM from transgenic mice expressing eGFP under control of the α-actin promoter were isolated at day 13.5-15.5 p.c. IPSCM and FCM were injected into adult mouse hearts (2 injections, ∼500,000 cells per site). 6-12 days after transplantation, recipients were sacrificed and viable ventricular tissue slices (thickness: 150 μ m) were prepared. Slices were focally stimulated by a unipolar electrode placed in host tissue. AP recordings were performed by glass microelectrodes in transplanted cells, which could be identified by their green fluorescence, and in neighboring host tissue within the slices. Results: Coupling of iPSCM and FCM to host tissue could be clearly demonstrated, 74% of iPSCM and 85% of FCM were coupled. Some transplanted iPSCM and FCM had no conduction blocks even at high stimulation frequencies up to 8 Hz, while others had blocks at lower frequencies. The delay between stimulus and AP upstroke was significantly longer in iPSCM (35.34±8.79 ms) than in FCM (19.84±3.77 ms). In host tissue, the delay was 6.96±1.0 ms. IPSCM had immature AP properties at all time points, while FCM matured and possessed comparable AP properties as host cardiomyocytes after 12 days. Conclusions: IPSCM and FCM are able to integrate electrically into host tissue, but conduction blocks and decelerations occur. The quality of integration is higher in FCM than in iPSCM. AP properties of transplanted iPSCM differ considerably from those of host cardiomyocytes up to day 12 after transplantation, while FCM mature to an adult electrophysiological phenotype.