Myocardial infarction model and cell/patch delivery

All animal studies were approved by Animal Care and Use Committee in the Catholic University of Korea. We have complied with all relevant ethical regulations for animal testing and research. Fischer 344 rats (180–200 g, male, Orientbio, Korea) were anesthetized with 2% inhaled isoflurane and intubated via the trachea with an 18-gauge intravenous catheter. The rats were then mechanically ventilated with medical grade oxygen. Animals were placed on a 37 °C heating pad to prevent cooling during procedure. After shaving the chest, a left thoracotomy was performed. MI was achieved by tying a suture with sterile polyethylene glycol tubing (22 G) placed into the left anterior descending (LAD) artery for 1 min, and then the knot was permanently ligated using a 7–0 prolene suture. To establish baseline left ventricular function, the ejection fraction (EF) and regional wall motion abnormalities (RWMA) were examined post operation day (POD) 7 (inclusion criterion: EF <45% by echocardiographic evaluation). On the same day, rats were anesthetized again using isoflurane inhalation, intubated and mechanically ventilated. The animal chest was re-opened, and the pericardium was partially removed from the infarcted heart. Then, hiPSC-CMs (1.0 × 10⁶ per rat) were injected at two different sites in the border zone of infarcted myocardium and the hMSC-PA was implanted directly on the epicardium using two sutures (Supplementary Movie ³). To trace the injected hiPSC-CMs within the heart tissues, we used CM-DiI (Chloromethlybenzamido, CellTracker ^TM). The stock solution was prepared using a modification of the manufacturer’s instructions. From a 1 mg/ml CM-DiI stock solution in DMSO, 5 μM solutions were made in 500 μl of the DMEM and this working solution was used to label the hiPSC-CMs. The chest was closed aseptically, and antibiotics and 0.9% normal saline solution was given. All rats received following immunosuppressants (azathioprine, 2 mg/kg; cyclosporine A, 5 mg/kg; methylprednisolone, 5 mg/kg) daily.