Transplantation of vascularized cardiac microtissue from human induced pluripotent stem cell cells improves impaired electrical conduction in a porcine myocardial injury model

Abstract

OBJECTIVE: To demonstrate that the transplantation of human induced pluripotent stem cell (hiPSC)-derived vascularized cardiac microtissue (VCM) can improve conduction disturbances after myocardial injury (MI). METHODS: We prepared cell sheet-shaped VCM with hiPSC-derived cardiomyocytes and vascular cells using dynamic rocking culture. We induced MI via epicardial cryoablation in immunosuppressed crown minipigs (VCM and sham groups; n = 3) and transplanted the VCMs immediately after MI induction. The pigs underwent epicardial electroanatomical mapping immediately before and 1 week after MI induction. RESULTS: One week after MI induction, mean electrical potentials at the MI site decreased in both groups during sinus rhythm (from 11.05 to 1.74 mV in the VCM group and from 8.72 to 2.70 mV in the sham group, P = .048). The mean conduction velocity between the remote and MI sites was numerically higher in the VCM group compared with the Sham group (2.84 m/s vs 1.74 m/s). One of the 3 animals in the VCM group demonstrated 2 independent origins of excitation corresponding to the pacing sites when simultaneous pacing of the remote and MI sites was performed 1 week after MI induction. Histologic examination confirmed that the VCM had engrafted on the surface of the MI region. Furthermore, we confirmed that the myocardial tissue in the MI region remained more intact one week after injury in the VCM transplantation group compared to the sham group, suggesting that this contributed to the reduction of conduction disturbances. CONCLUSIONS: The transplantation of VCM demonstrated a potential for improving conduction disturbances in MI.