Effect of Cardiac Stem Cells on Left-Ventricular Remodeling in a Canine Model of Chronic Myocardial Infarction

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Abstract

Background—

Regenerative medicine, including cell therapy, is a promising strategy for recovery of the damaged myocardium. C-kit–positive cardiac stem cells (CSCs) have been shown to improve myocardial function after ischemic injury in animal models and in early clinical experience. We used a chronic large animal model of myocardial infarction with substantial reductions in left-ventricular (LV) ejection fraction and adverse remodeling to examine the effect of late autologous CSC intramyocardial injection on long-term cardiac structure and function.

Methods and Results—

Thoracotomy and ligation of the proximal left anterior descending artery, additional diagonal branches, and atrial biopsy for CSC culture were performed in canines. Baseline cardiac MRI was performed at 6 weeks postinfarct followed by repeat thoracotomy for randomization to intramyocardial injection of CSCs (n=13) or vehicle alone (n=6). At 30 weeks postmyocardial infarction, repeat MRI was performed. Data were analyzed using nonparametric tests (Wilcoxon signed-rank and rank-sum tests). In control animals, LV end-systolic volume and end-diastolic volume increased from 6 to 30 weeks (median and interquartile range, 51.3 mL [43.3–57.4] to 76.1 mL [72.0–82.4]; P=0.03 and 78.5 mL [69.7–86.1] to 99.2 mL [97.1–100.4]; P=0.03). Left-ventricular ejection fraction declined further (35.2% [27.9–38.7] to 26.4% [22.0–31.0]; P=0.12). In the cell-treated animals, this late adverse LV remodeling was attenuated (LV end-systolic volume, 42.6 mL [38.5–50.5] to 56.1 mL [50.3–63.0]; P=0.01 versus control). There was a nonsignificant attenuation in the increase in LV end-diastolic volume (64.8 mL [60.7–71.3] to 83.5 mL [74.7–90.8]; P=0.14 versus control) and LV ejection fraction change over time differed (30.5% [28.4–33.4] to 32.9% [28.6–36.9]; P=0.04 versus control).

Conclusions—

Intramyocardial injection of autologous CSCs in a late phase model of chronic infarction resulted in less increase in LV end-systolic volume and preservation of LV ejection fraction.

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