Abstract 314: Allogeneic Cortical Bone Stem Cells Preserve Cardiac Structure and Function by Inhibition of Cell Death and Enhancing Angiogenesis in the Swine Heart After Myocardial Infarction

Abstract

Introduction: Novel therapies are needed to improve cardiac function after MI; one strategy is to replace lost myocardium. Despite the success of bone marrow- and cardiac- stem cell clinical trials, we’re still searching for the optimal stem cell type most suitable for cardiac regeneration. Previously, we described a novel cell population derived from the cortical bone (CBSCs) which repaired the heart post MI via transdifferentiation and paracrine signaling mechanisms in a mouse model. In the present study, we evaluate the translational potential of allogeneic CBSCs in swine MI model. Hypothesis: Intramyocardial injection of CBSCs into the MI border zone immediately after reperfusion will preserve cardiac structure and pump function by enhancing endogenous repair through secretion of paracrine factors. Methods & Results: Female Göttingen minipigs received MI via occlusion of the left anterior descending coronary artery (LAD) for 90 minutes, followed by reperfusion. Animals received either 20 million CBSCs (via 10 intramyocardial injections) or saline injections. Cardiac structure and function was evaluated using echocardiography at baseline and 4 weeks post-MI. During the 4 weeks after MI there was depression if pump function in saline treated group (EF: 69.27% ± 1.92 [baseline] to 46.305% ± 3.53 [4 weeks post MI] p<0.0001 ) and dilation of the LV (EDV: 39.01 ml ± 3.47 [baseline] to 51.5 ml ± 5.67 [4 weeks post MI] and ESV was 13.71 ml ± 2.47 to 27.72 ml ± 3.86 ( p= 0.0136 ). The MI + CBSC group had no significant change in ventricular pump function from baseline to 4 weeks post-MI; while demonstrating preservation of cardiac structure indicating a decrease in ventricular remodeling/scar formation. A decrease in TUNEL+ cells and an increase in angiogenesis was also observed in CBSC’s treated animals. Conclusion: CBSC’s appear to reduce infarct expansion by reducing post MI myocyte death and by increasing angiogenesis. These data show that administration of CBSCs immediately after reperfusion of an infarcted region of the heart can reduce adverse cardiac remodeling and improve cardiac function.