Abstract 14851: Retention of Differentiated Cardiac Stem Cells 1-Year After Intracoronary Cell Delivery in Rats With Acute Myocardial Infarction
We have previously reported that intracoronary infusion of c-kit+ cardiac stem cells (CSCs) improves LV function and structure at 1 year after myocardial infarction (MI). However, it is unknown whether CSCs persist and differentiate into cardiac myocytes 1 year after transplantation. To address this issue, female rats received intracoronary vehicle or 1x106 syngeneic male CSCs 4 hours after a 90-min coronary occlusion. Y-chromosome (Y-Chrms) was detected by FISH to evaluate transplanted CSCs in recipient female hearts (n=5). Cardiac myocytes were identified by α-sarcomeric actin (α-Src). In each heart, 25 confocal images (355 μm2) were analyzed (6 from scar area, 14 from border zones, 5 from noninfarcted area) and results were normalized to male heart Y-Chrms density. At 1 year after CSC transplantation, we found retention of Y-Chrms+ cells in the scar area (9.8±1.6% of total nuclei), border zone (6.8±1.1%), and noninfarcted area (3.8±0.9%) (Figs. A-D). Double positive (Y-Chrms+ and α-Src+) cells were 7.4±1.4% of nuclei in scar area, 3.7±0.7% in border zone, and 0.5±0.2% in noninfarcted area, demonstrating differentiation of CSCs into new cardiac myocytes (Fig. E). Most newly-formed Y-Chrms+ myocytes were mononucleated and small with partially aligned myofibrils, resembling late fetal/neonatal cells; however, a few mature large Y-Chrms+ myocytes were found in the risk region (white arrows in Figs. B, C). The ratio of Y-Chrms+ myocytes to total Y-Chrms+ cells was greater in the scar than in border zone (74.3±2.1% vs. 54.3±2.9%, Fig. F). These data indicate, for the first time, that transplanted CSCs persist and differentiate into new myocytes at 1 year after intracoronary delivery in a model of acute MI. However, even at 1 year, most CSC-derived myocytes are small and do not resemble mature myocytes; their number is not sufficient to fully account for the functional improvement previously reported at 1 year, suggesting that other mechanisms (e.g., paracrine) are at work.
- © 2013 by American Heart Association, Inc.