Abstract 1270: Enhancing Efficacy of Cell Transplantation in Hearts with Post-infarction LV Remodeling by an Injectable Biomatrix
Bone marrow-derived mononuclear cell (BMNC) transplantation provides the possibility of rescue or regeneration of myocardium lost during acute myocardial infarction (AMI). Although it is a consistent observation in the literature that cellular transplantation improves LV contractile function, the cell engraftment rate a few weeks after the transplantation is usually extremely low. It is clear that the majority of cells transplanted to the heart do not demonstrate sustained engraftment. Therefore, methods to enhance the rate of stem cell engraftment and proliferation, and to direct the fate of engrafted BMNCs are urgently needed. We investigated whether delivery of BMNCs by an injectable 3D porous PEGylated fibrin biomatrix that covalently binds hepatocyte growth factor (HGF) will enhance the rate of cell engraftment and provide functional benefit. Our delivery system is an injectable PEGylated fibrin biomatrix that covalently binds HGF and entraps cells. Thirty-six Balb/C female mice with AMI secondary to LAD ligation were randomly assigned to 1 of 4 groups: the Control group (C, n=8) received a saline (50μl) myocardial injection; Cell group (n=10), 500,000 murine BMNCs were suspended in 50μl saline and injected into myocardium of the peri-infarct and infarct zone; the Biomatrix+HGF (n=9); and Biomatrix+HGF+Cell (n=9) group hearts received injectable biomatrix (identical volume) with or without entrapped BMNCs. All animals were sacrificed 4 weeks after AMI and transplantation for immnohistochemical evaluation of angiogenesis, apoptosis and fibrosis. The LV ejection fraction was significantly higher in each treatment groups (echocardiography) compare to C group at day 14 and 28 post MI. Engraftment rate increased 15 fold in hearts receiving the Biomatrix-HGF+cell delivery (p<0.01), which was accompanied by the lowest levels of apoptosis and highest LV contractile function recovery among the treated groups. Thus, the injectable HGF modified PEGylated fibrin biomatrix provides a vehicle for cell and growth factor delivery that acts synergistically to enhance BMNC transplantation efficacy.