Abstract 15649: Human Induced Pluripotent Stem Cell-Derived Cardiac Fibroblast Assembled Extracellular Matrix Rescues Cardiac Function in an Acute Myocardial Infarction Mouse Model

Background: Acute myocardial infarction (AMI) is the leading cause of heart failure (HF). Therapies to curb post-AMI pathological left ventricular remodeling could reduce the burden of HF. Human iPSC derived cardiac fibroblast assembled extracellular matrix (iCFX) is a novel acellular biomaterial that consists of a unique blend of extracellular matrix proteins with tissue reparative potential. We hypothesize that direct cardiac injection of iCFX into the peri-infarct border in a mouse AMI model will restore cardiac function and reduce pathological remodeling.

Methods: Acute MI was induced by permanent ligation of the left anterior descending coronary artery in 10-week immunocompetent C57BL/6 mice. iCFX was supplied by Cellular Logistics Inc, Madison, WI. One day post-AMI, mice were randomly treated with a 50 microliter epicardial injection of either PBS control, 1 mg iCFX or 10 mg iCFX. Baseline and 28-day echo were performed.

Results: At baseline, there were no differences in any echo parameter between treatment groups. By 28 days post treatment, mice treated with 10 mg iCFX had increased ejection fraction ((25.8+/-3.1% (n=8) vs. (13.9+/-1.8% (n=11) p=0.001), fractional shortening ((15.5+/-2.0% (n=8) vs. 6.9+/-1.3%) (n=11) p=0.003), and cardiac output (16.0+/-2.3 ml/min (n=8) vs. 9.7+/-1.2 ml/min (n=11) p=0.002) compared to placebo treated animals. The 1 mg dosing group showed non-significant improvements in contractility parameters. Reduced end systolic and end diastolic volumes in the 10 mg group was observed, but these were not statistically significant.

Conclusions: Therapeutic administration of human iCFX was associated with significant improvements in left ventricular contractility following AMI in an immunocompetent mouse model. Furthermore, a clear dose response pattern was observed.