Abstract 2042: What is the Best Technique to Inject Stem Cells and the Optimal Dose of Stem Cells for the Treatment of Myocardial Infarction?
There is no consensus regarding the best technique to inject stem cells or the optimal dose of stem cells to inject for the treatment of myocardial infarction. We determined the effects of human umbilical cord blood mononuclear stem cells (HUCBC) on infarction size, in doses of 5×105, 106, 2×106, 4×106, 8×106, 1.6 ×107 and 3.2×107 in saline directly injected into the myocardium (IM), or injected into the transiently clamped ascending aorta to facilitate coronary perfusion (IA), or injected intravenously (IV) in 84 anesthetized Sprague-Dawley rats with permanently ligated left anterior descending coronary arteries. Each HUCBC dose was given to 4 rats by each technique (IM, IA, IV) ≤2 hours after coronary ligation. Four to six infarcted rats treated with saline alone by each technique served as controls. No rat received immunosup-pressive therapy. Infarct size in each rat was determined at 1 month after coronary ligation by tetrazolium staining and computer imaging software.
RESULTS: Infarct size in untreated rats averaged 25±2% of the LV muscle area. IM HUCBC reduced infarct size by 73 to 95% in comparison with controls (p<0.002). IA HUCBC reduced infarct size by 46 to 86% (p<0.03), and IV HUCBC reduced infarct size by 53 to 80% (p<0.02) compared with controls. See FIGURE⇓. IM HUCBC produced the greatest Infarct size reduction with IM HUCBC treated infarcts 10 –27% smaller than IA (p<0.02) and 18 –20% smaller than IV (p<0.04). The optimal HUCBC dose for maximal infarct size reduction for each technique was 4X106 IM, 8X106 IA, and 3.2X107 IV. Intramyocardial, IA, or IV HUCBC all significantly reduce myocardial infarction size without requirements for host immunosuppression.