Abstract 228: Injectable Delivery of Mesenchymal Stem Cells in Fibrin For Therapeutic Repair of Chronic Myocardial Infarction
Despite advancements in treating myocardial infarction, therapies that improve the structural and functional capacities of the myocardium remain lacking. Previous studies have demonstrated that fibrin biopolymer provides structural support and promotes cellular growth, and mesenchymal stem cells (MSCs) can secrete growth factors to stimulate angiogenesis. We hypothesized that the combined delivery of MSCs and fibrin would synergistically enhance cardiac function and angiogenesis. To test this hypothesis, nude (rnu homozygous) rats underwent occlusion of the left anterior descending coronary artery for 17 min followed by reperfusion. Treatments of 2 X 106 human MSCs in 0.5% bovine serum albumin (BSA), MSCs in fibrin, fibrin, or BSA were injected into the infarct area of the left ventricle (LV) at five weeks post-MI (n=9 per group). The hearts were excised five weeks later and cryosectioned for histological analysis. Additionally, echocardiography was performed pre-injection and pre-euthanasia for LV internal diameters and fractional shortening as measures of cardiac function. Immunohistochemical staining for anti-CD31 demonstrated that the MSCs in fibrin group had significantly higher microvascular density (310±35 per mm2) in comparison to both BSA (170±23 per mm2) and fibrin (158±17 per mm2) groups (P<0.05), whereas the MSCs group was not significantly different from the controls. Anti-alpha-smooth muscle actin staining revealed that the MSCs in fibrin group also had significantly higher arteriole density (13±2 per mm2) compared to both BSA (8±1 per mm2) and fibrin (8±1 per mm2) groups (P<0.05), whereas the MSCs group was not significantly different from controls. Echocardiography results showed that LV internal diameters significantly worsened in the control BSA group from pre-injection to 5 weeks post-injection during diastole (6.8±0.2 mm vs. 7.5±0.2 mm, P<0.05) and systole (4.7±0.3 mm vs. 5.1±0.3 mm, P<0.05), whereas there were no significant differences among the other groups. Fractional shortening was not significantly different for any treatment. In conclusion, our data demonstrates that MSCs in fibrin synergistically enhanced neovascularization within the infarct and prevented LV cavity dilation.