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 bioabsorbable 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). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed.

RESULTS

Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak left ventricular velocity]). 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 < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), β-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.