Abstract 4221: Stromal Cell-Derived Factor-1α Activation of Tissue Engineered Endothelial Progenitor Stem Cell Matrix Enhances Ventricular Function After Myocardial Infarction by Inducing Neovasculogenesis
Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor stem cells (EPC) have been shown to ameliorate this process, particularly when activated with Stromal Cell-Derived Factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that surgical implantation of a tissue engineered extracellular matrix scaffold seeded with EPCs primed with SDF could induce borderzone (BZ) neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after MI. EPCs were isolated, characterized, cultured on a vitronectin/collagen scaffold, and primed with SDF to generate the activated stem cell matrix (SCM). Rats (n=44) underwent LAD ligation to induce MI. SCM was sutured to the anterolateral LV wall overlying the region of ischemia. Control animals received sutures but no SCM. At four weeks, BZ VEGF levels were assessed by immunoblotting, vessel density was quantified by immunohistochemical microscopy, and microvascular perfusion was measured by lectin microangiography. Ventricular geometry and infarct fraction were assessed by digital planimetric analysis of sectioned hearts. LV function was evaluated by echo, P-V conductance, and Doppler flow. BZ VEGF and neovasculogenesis were both significantly increased in the SCM group (4.1 vs 6.2 vessels/HPF, p<.01). BZ perfusion was enhanced four-fold as evidenced by lectin microangiography (.7 vs 2.7 % vessel volume/section volume, p=.04). Digital planimetry exhibited significantly preserved LVID (9.7mm vs 8.6mm, p=.005) and reduced infarct scar formation expressed as percent of total section area (16 vs 7%, p=.002). SCM animals showed a significant preservation of function as measured by three separate modalities. Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after MI.