Abstract 15555: Administration of c-Kit+ Cardiac Stem Cells (CSCs) Results in Increased Proliferation and Cardiac Content of CSCs 1 Year Later
Background: We have previously shown in rats that the beneficial effects of c-kit+ CSCs on LV function and remodeling post-myocardial infarction persist for at least 1 year after CSC administration. However, in that study the retention of transplanted Y-chromosome+ cells in the risk region (RR) of female rat hearts at 1 year was low (<10% of total nuclei) and not sufficient to account for the functional improvement, suggesting that other mechanisms must be at work.
Methods and Results: To address this issue, rats received intracoronary vehicle or 1x106 syngeneic CSCs 4 h after a 90-min coronary occlusion; 11 months later, BrdU treatment was given for 1 month. CSCs, which are c-kit+/CD45−, were distinguished from c-kit+ hematopoietic stem cells/mast cells, which are CD45+. At 1 year after CSC administration, the total number of c-kit+ or c-kit+/BrdU+ cells in the heart (the sum of c-kit+/CD45− and c-kit+/CD45+ cells) did not differ between CSC and control groups (Figs. H and I). However, CSC transplantation resulted in increased numbers of CSCs (c-kit+/CD45− cells) in the RR (i.e., the infarct zone plus border zone)(47.6±7.0% of total c-kit+ cells vs. 27.9±4.1% in vehicle group; n=5, P<0.05; Fig. J). Among CSCs (c-kit+/CD45− cells), the fraction that was newly formed (c-kit+/CD45−/BrdU+) was dramatically increased in the RR of the CSC group (+ 2.6-fold vs. vehicle group; n=4, P<0.05; Fig. M), indicating increased CSC proliferation and turnover.
Conclusions: These data reveal, for the first time, that a single intracoronary infusion of CSCs is followed by an increase in both the proliferation and the total number of c-kit+ CSCs in the myocardium that persists, surprisingly, for at least 1 year after cell delivery. Since transplanted cells do not differentiate into adult myocytes, these data suggest that the long-term salubrious effects of CSCs on cardiac function are mediated by sustained activation of the CSC pool in the heart.
Author Disclosures: Q. Li: None. N. Chen: None. L. Luo: None. Q. Ou: None. W. Xie: None. G.N. Hunt: None. X. Tang: None. G.D. Rokosh: None. R. Bolli: None.
- © 2014 by American Heart Association, Inc.