Abstract 1262: Elastic, Biodegradable Cardiac Patch Implantation Induces Embryonic-like Cellularization In The Post-infarct Ventricular Wall
Background: The limited capacity for damaged myocardium to regenerate cardiomyocytes is a major barrier to the restoration of cardiac function. A promising approach may rely on development of techniques to trigger cardiomyocyte regenerative responses. Recently we reported that elastomeric, biodegradable, polyester urethane urea (PEUU) patch implantation onto sub-acute left ventricular (LV) infarcts induced abundant muscle bundles, which were positive for alpha-smooth muscle actin (SMA), under PEUU implantation area. Patching prevented LV dilatation and improved contractile function. In the present study, we tested the hypothesis that these muscle cells had the potential for cardiomyocyte regeneration.
Methods: 2 weeks after proximal left coronary ligation in Lewis rats, infarcted LVs were covered with PEUU patches or had sham surgery. Histological assessment was performed 8 weeks after patching and cardiac function was monitored longitudinally by echocardiography.
Results: Regional contraction of patched areas increased as well as the global contraction with prevention of further diastolic dilation. Cardiac transcription factors Nkx-2.5 and GATA-4 were expressed in the SMA positive cells. Cardiac specific troponin-T and alpha-sarcomeric actinin were expressed in striated patterns similar to nascent cardiomyocytes and co-localized with SMA. We further investigated SMA expression in embryonic mouse ventricles and found sarcomeric actinin co-localized with SMA at embryonic day 11.5, which was analogous with the muscle bundles seen in the patched ventricles.
Conclusion: Patching post-infarct myocardium with PEUU improved cardiac function and lead to cellularization with phenotypic expression similar to that of the embryonic ventricular wall.