Electrical Integration Promotes Maturation of Transplanted Cardiomyocytes

Electrical integration and maturation of transplanted immature cardiomyocytes are essential to enhance functional benefit and reduce arrhythmogenic risk. Yet, little is known about the time course of integration and maturation. Methods: Fetal cardiomyocytes (12.5-15.5 days p.c.) expressing eGFP were transplanted into cryoinjured non-transgenic adult mouse hearts. At 6, 9 and 12 days after transplantation, viable tissue slices of recipient hearts (thickness 150 mu m) were prepared and intracellular action potentials of transplanted and host cardiomyocytes within the slices were recorded by sharp glass electrodes. Analyzed cells were marked by tetramethylrhodamine injections via the recording pipette, transplanted cells were identified by their green/red dual fluorescence. Slices were stimulated by a unipolar electrode placed in healthy host tissue. Results: In transplanted cells coupled to healthy host myocardium, action potential duration at 50% repolarization (APD50), which decreases during native murine development, decreased from 32.2 plus or minus 3.3 ms (day 6) to 27.9 plus or minus 2.6 ms (day 9) and 19.6 plus or minus 1.6 ms (day 12). The latter value was equal to the APD50 of host cells (20.5 plus or minus 3.2 ms, P = 0.78), whereas cell size of transplanted cardiomyocytes was considerably smaller compared to host cardiomyocytes. The maximal stimulation frequency without conduction blocks, which was regarded as indicator of the quality of electrical integration of transplanted cells, was inversely proportional to the APD50 at 2 Hz (r super(2) = 0.59). In transplanted cells embedded in the cryoinjury, which showed no electrical integration, APD50 was 59.2 plus or minus 4.3 ms at day 12. Conclusions: Electrical maturation of transplanted cardiomyocytes is a time-dependent process, depending on the quality of electrical integration.