Abstract 17942: Functional Consequences of a Tissue-Engineered Myocardial Patch for Cardiac Repair in a Rat Infarct Model
This study evaluates the capacity of an aligned, fibrin-based, stretch-conditioned cardiac patch to ameliorate left ventricular (LV) remodeling in the acute phase post-infarction. Cardiac patches were constructed from native (CM+) and cardiomyocyte-depleted (CM-) neonatal rat heart cell populations entrapped in a fibrin gel. Patches were exposed to 7 days static culture and 7 days cyclic stretching prior to implantation onto the LV epicardium of syngeneic, immunocompetent rats that had received a permanent ligation of the LAD coronary artery. Prior to implantation, the ECM of both patches remained primarily fibrin but entrapped cells had begun to deposit ECM proteins, with increased collagen deposition occurring in CM+ patches. CM+ patches generated measurable contractile forces (2.5±0.8mN) both spontaneously and in response to pacing. Vascular structures were found inside the patch after 3 days in vivo. After 4 weeks in vivo, the patches had been remodeled into a collagenous tissue and live, elongated donor cardiomyocytes were found within the engrafted CM+ patches. Non-cardiomyocyte cell migration from the CM+ patch into the host myocardium was found after both 1 and 4 weeks in vivo. Significant improvement in cardiac contractile function was seen with the administration of the CM+ patch (EF increased from 35.1±4.0% for MI only to 58.8±7.3% with a CM+ patch, p<0.05) associated with a 77% reduction in infarct size (61.3±7.9% for MI only, 13.9±10.8% for CM+ patch, p <0.05), and the elimination of LV free wall thinning. This decrease in infarct size was evident as early as 3 days post-ligation with the CM+ patch. Decreased infarct size and reduced wall thinning also occurred with the administration of the CM- patch (infarct size 36.9±10.2%, LV wall thickness: 1058.2±135.4μm for CM- patch, 661.3±37.4μm for MI only, p<0.05), but without improvements in cardiac function. Improvements in contractile function and the substantial reduction of infarct size are likely a result of paracrine effects, due to the separation of donor CMs from the host myocardium and thin dimension of the patches. These beneficial effects seen in a patch containing CMs indicate the effects are dependent upon cellular communication between cardiomyocytes and non-myocyte cardiac cells.
- © 2013 by American Heart Association, Inc.