Abstract 3039: Local Injection of Anti-c-kit Antibody Enhanced Myocardial Homing of Stem Cells and Improved Heart Function
Objective: Emerging evidence suggests that stem cells protect the myocardium from ischemic injury and promotes beneficial remodeling. However, stem cells therapy for myocardial regeneration is limited by the number of stem cells that migrate to, engraft in, and proliferate at sites of injured myocardium. In the present study, we evaluated the homing of c-kit positive cells, angiogenesis and functional improvement after intracardiac injections of anti-c-kit antibody in rat left anterior descending (LAD) ligation model.
Methods: Adult Lewis rats (n=19) was randomly divided into 3 group as sham (n=6), myocardial infarction (MI) treated with anti-c-kit antibody (n=7) and treated with PBS (n=6). 2.5μg anti-c-kit antibody or PBS were injected in a total volume of 250ul at five injection sites into anterior and lateral aspects of the viable myocardium bordering of the infarction. Left ventricular function was assessed by pressure-volume loops. Infarct size, angiogenesis and c-kit positive homing were evaluated by histochemical staining and qualitative real time PCR.
Results: MI-anti-c-kit hearts exhibited smaller infarction size (13.10±1.45% vs. 19.75±1.51%, n=6 –7, p<0.05) and higher capillary density (137.4±4.6 vs. 115.3±6.0 vessels per high power field (HPF) (400×), n=5, p<0.01) than MI-PBS hearts. Immunohistological analysis and quantitative real-time PCR measurement revealed that intramyocardial injection of anti-c-kit antibody significantly enhanced myocardial homing of c-kit positive cells compared to animals with PBS injections (38.3±5.3 vs. 25.7±1.5 c-kit+ cells per HPF (630×), n=5, p<0.05). Compared to PBS treated myocardial infarction group, local injection of anti-c-kit antibody significantly improved cardiac function (dp/dt max, dp/dt min, EF; n=6 –7, p<0.05) assessed by pressure-volume loops after 4 weeks.
Conclusion: Local injection of anti-c-kit antibody could enhance the homing of c-kit+ cells to the infarcted heart and may have values for mediating substantial functional recovery after acute myocardial infarction.