Abstract MP205: Human Induced Pluripotent Stem Cell Derived Cardiomyocyte And Fibroblast Patch To Treat Heart Failure
Background: We tested a tissue engineered (TE) patch composed of a biodegradable mesh embedded with human neonatal fibroblasts and seeded with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to treat heart failure in Yucatan mini swine receiving no immune suppression. Methods: Swine (N=12) underwent a 90-minute balloon occlusion/reperfusion of the left anterior descending coronary artery to create a myocardial infarction (MI). Following a 4-week recovery, the TE patch was implanted via a mini median sternotomy. The following were obtained: Cardiac Magnetic Resonance (CMR) imaging, cardiac catheterization, activity monitoring with FitBark collars, treadmill testing, 24/7 ECGs with implanted loop recorders. Results: At 4 weeks after MI, swine had increased left ventricular (LV) volumes, decreased end-systolic elastance (Ees), a shift of the diastolic pressure/volume (P/V) to the right of baseline and an increase in the LV mass/volume. After 6 months of treatment, the TE treated swine (N=7) compared to inert tissue treated swine (N=5): End-systolic volume (2% decrease vs 18% increase); End-diastolic volume (7% decrease vs 26% increase): Ees (1.0±0.2 vs 1.9±0.2 mmHg/mL, P=0.006); the diastolic P/V loops shifted back toward baseline with no change in slope, and LV mass decreased. There was no mortality related to treatment; the TE patch was well tolerated as assessed by CMR and histology. The loop recorders showed TE treated animals remained in sinus rhythm throughout with no ventricular arrhythmias, no change in heart rate and a 20% increase in daily activity levels and a 20% increase in exercise tolerance. Conclusions: This TE patch with human neonatal fibroblasts and hiPSC-CMs improves LV function, partially reverses LV remodeling and improves exercise in non-immune suppressed swine with heart failure after 6 months of treatment.