Abstract 701: Optimization for the Timing of CD34+ Cell Transplantation Therapy in Acute Myocardial Infarction
Background: Recently, numerous clinical trials of autologous stem/progenitor cell transplantation therapy for myocardial infarction (MI) are ongoing. However, the outcomes vary depending on the timing of cell transplantation following the onset of MI. We tested the hypothesis that timing of cell transplantation may be critical to determine the cardiac functional recovery following MI.
Methods and Results: Nude rats were assigned in the following groups (n=6 in each group); human CD34+ cells (5×105/rat) were intravenously injected to the rats immediately (group D0), 3 days (group D3) and 7 days (group D7) after MI, and PBS was injected in the same manner for the control. Echocardiographic, hemodynamic and histological analyses were performed 28 days after the treatment. In the echo analysis, the group D3 exhibited the best-preserved LV function among the all groups. The group D3 also exhibited the best result in the hemodynamic study. Being consistent with these results, the fibrosis area of LV was significantly reduced with high capillary density in ischemic border zone in the group D3 compared to that in the other groups. Next, we examined the recruitment and survival of the injected CD34+ cells in ischemic myocardium 1 day and 14 days after the treatment by immunohistochemistry using an anti human nuclear antigen (HNA) antibody. Interestingly, although there were no significant differences in the HNA+-survived CD34+ cell number among the three groups, the group D3 exhibited the greatest HNA+/CD34+-cell recruitment in ischemic myocardium. Moreover, endogenous EPC mobilization in peripheral blood assessed by EPC culture assay was also greater in the group D3 than that in the other groups 7 days after the exogenous CD34+ cell injection.
Conclusion: The timing of day 3 after MI exhibited the most beneficial effects on cardiac functional recovery following MI, at least in part, via a mechanism for the synergistic effect of exogenous CD34+ cell and endogenous bone marrow-derived EPC contribution to the cardiac functional recovery. Our data suggest that the timing of cell transplantation may be a critical factor to obtain better clinical outcomes in autologous stem/progenitor cell transplantation therapy for ischemic heart diseases.