Abstract 18373: In Vitro Model of Allogenic Cell Transplantation for Conduction Defects - Electrical Coupling Between Rat iPS Cell-Derived Cardiac Cells and Rat Native Cardiac Cells
Introduction: Development of novel therapeutic strategies for bradyarrhythmias has drawn substantial attention. However, clinical applications have not yet been achieved. Whether the transplantation of stem cell-derived cardiomyocytes could repair conduction defects has remained to be elucidated. Here we report in vitro transplantation of allogenic stem cell-derived cardiac cells restored the electrical propagation in the in-vitro cardiac conduction block model of rats.
Hypothesis: Rat induced pluripotent stem cell-derived cardiac cells (riPSC-CC) repair cardiac conduction disturbances.
Methods: Cardiac cells were derived from rat iPS cells using an embryoid body-based differentiation method with the serial application of growth factors (GF); Activin A, BMP-4 and IWP-2. Isolated neonatal rat ventricular cardiomyocytes (NRVM) were cultured in the two discrete regions to mimic cardiac conduction defects on multiple-electrode dishes (MED64), then, riPSC-CCs were seeded in the lane between the two discrete regions. Both spontaneous and pacing-induced electrical propagation properties between riPSC-CCs and NRVMs were analyzed by field potentials, Ca transients and action potentials.
Results: Flow cytometric analysis showed 74.0 +/- 2.7% of riPSC-CCs expressed cardiac troponin T (n=3). Immunostaining analysis displayed organized sarcomeric structure in riPSC-CCs and the expression of Cx43 between riPSC-CCs and NRVMs. Membrane potential imaging with di-8-ANEPPS revealed electrical impulse propagated from one NRVM region to the discrete NRVM region through riPSC-CCs pathway. RiPSC-CCs exhibited significantly longer action potential duration compared to that of NRVMs (276 +/- 7.9 vs 215 +/- 7.7 msec respectively, n = 6). Electrophysiological studies using MED64 system demonstrated that the conduction time (CT) and the functional refractory period (FRP) of riPSC-CCs pathway were prolonged compared to those of NRVMs (109 +/- 8.9 msec, 186 +/- 14 msec respectively, n=14).
Conclusions: RiPSC-CCs showed electrical coupling between two discrete regions of NRVMs. The CT and the FRP of riPSC-CCs pathway were prolonged compared to those of NRVMs.
Author Disclosures: A. Yoshida: None. J. Lee: Research Grant; Modest; Astellas Pharma Inc., Takeda Pharmaceutical Inc, Daiichi Sankyo Inc.. Research Grant; Significant; Grants-in-Aid for Scientific Research of JSPS, Shionogi Pharmaceutical Inc.. Honoraria; Modest; Kowa Pharmaceuticals Inc., Sumitomo Dainippon Pharma Co. Ltd. S. Miyagawa: None. Y. Sawa: None. Y. Sakata: None. I. Komuro: None.
- © 2016 by American Heart Association, Inc.