Human Induced Pluripotent Stem Cell Derived Cardiomyocyte Patch in Rats with Heart Failure

BACKGROUND: To treat chronic heart failure (CHF), we developed a robust, easy to handle bio absorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue.

METHODS: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (N=12) or left coronary artery ligation (N=45). Three weeks after ligation CHF rats were randomized to either CHF control with sham thoracotomy (N=21) or had a fibroblasts/hiPSC-CMs patch (N=24) implanted. In addition, all sham surgery rats obtained a sham thoracotomy. Three weeks after randomization hemodynamics, echocardiography, electrophysiologic and cell survival studies were performed.

RESULTS: Patch treated rats had decreased (P<0.05) left ventricular end diastolic pressure, the time constant of LV relaxation (Tau), increased anterior wall thickness in diastole and improved echo derived indices of diastolic function (E/e' and e'/a'). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P<0.05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction alpha-1 protein (connexin 43), beta-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart.

CONCLUSIONS: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.