Abstract 16529: Intracoronary Infusion of GCSF-Mobilized Human CD34+ Cells Preserves Left Ventricular Function and Prevents Infarct Expansion in a Swine Model of Acute Myocardial Infarction
Background: A phase I clinical trial revealed the safety and potential efficacy of intracoronary (i.c.) infusion of bone marrow (BM) CD34+ cells in patients with acute myocardial infarction (AMI). The final results of the “PreSERVE AMI” randomized phase II trial will be obtained this year. Despite such clinical development, CD34+ cell therapy for AMI has been preclinically investigated in the rat and mouse models, but not large animals.
Methods: AMI was induced by 60 min-balloon inflation and reperfusion in the left anterior descending artery of the farm swine. One week after AMI, swine were randomly allocated to receive i.c. infusion of 2х105/kg GCSF-mobilized human CD34+ cells (cell group, n=8) or saline (control group, n=7). Immunosuppression was maintained by intramuscular injection of cyclosporine daily from week 1 to 5. Magnetic resonance imaging was performed to assess cardiac function and infarct size at week 1 and 5. All swine were sacrificed at week 5. Chemical staining for isolectin B4 was performed to detect capillaries in the cardiac tissue.
Results: Left ventricular ejection fraction (LVEF) significantly increased in cell group (42.9±5.2 at week 1 to 48.5±4.1% at week 5, p<0.05) but not control group (47.6±2.4 to 44.8±3.5%, p=NS). LV end-systolic volume (LVESV) decreased in cell group (38.3±4.9 to 31.4±5.3 ml, p<0.01) but not control group (35.4±5.4 to 37.7±5.4 ml, p=NS). Regional wall thickening (RWT) in the border zone increased in cell group (30.8±14.9 to 45.5±10.4%, p<0.01) but not control group (37.2±16.4 to 26.4±9.3%). Infarct size by delayed enhancement increased in control group (16.8±7.5 to 22.35±6.4% of LV mass, p<0.05) but not cell group (20.5±10.2 to 20.87±8.0%). Changes in LVEF, LVESV and RWT between week 1 and 5 were better preserved in cell group than control group (p<0.05, 0.05 and 0.01, respectively). Histological capillary density in border zone was greater in cell group than control group (1698.0±474.2 vs 998.6±269.6/mm2, p<0.01).
Conclusions: Human CD34+ cell therapy may preserve global and regional LV function and prevent infarct expansion through enhancing neocapillary formation in swine with AMI. The favorable outcomes would support the further clinical development of the cell-based therapy in patients with AMI.
Author Disclosures: Y. Fujita: None. M. Kinoshita: None. H. Akimaru: None. E. Akimaru: None. M. Komatsu: None. Y. Furukawa: None. T. Asahara: None. A. Kawamoto: None.
- © 2014 by American Heart Association, Inc.