AIMS: Although mesenchymal stem cells (MSCs) show promising signs in reducing myocardial infarct (MI) size, the safety of endomyocardial delivery and the most efficacious dose is unknown. METHODS AND RESULTS: Three days after MI, female Yorkshire swine (25-32 kg, age 2 months, n = 32) were randomized to endomyocardial delivery of one of three MSC doses (2.4 x 10(7), 2.4 x 10(8), 4.4 x 10(8) cells) or vehicle control. Animals were sacrificed at 12 weeks. There were no safety issues related to cell delivery and all animals tolerated the procedure. By magnetic resonance imaging infarct size (g) was decreased in the experimental groups and increased in the control group; 2.4 x 10(7): Delta -2.5 +/- 2.5 g, 2.4 x 10(8): -0.9 +/- 2.71 g, 4.4 x 10(8): -1.6 +/- 5.8 g, and control +3.6 +/- 3.4 g (P = 0.002, P = 0.016, and P = 0.055 compared with control, respectively). There was no effect on ejection fraction or left ventricular volumes. By histology there were no toxic effects of MSC delivery, however, few engrafted MSCs were observed. CONCLUSION: Direct MSC delivery into infarcted myocardium was safe and produced a local but not a functional effect. There was no dose-dependent effect. The effect of MSCs on infarct reduction may result from transient residence and subsequent paracrine effects.
AIMS: Although mesenchymal stem cells (MSCs) show promising signs in reducing myocardial infarct (MI) size, the safety of endomyocardial delivery and the most efficacious dose is unknown. METHODS AND RESULTS: Three days after MI, female Yorkshire swine (25-32 kg, age 2 months, n = 32) were randomized to endomyocardial delivery of one of three MSC doses (2.4 x 10(7), 2.4 x 10(8), 4.4 x 10(8) cells) or vehicle control. Animals were sacrificed at 12 weeks. There were no safety issues related to cell delivery and all animals tolerated the procedure. By magnetic resonance imaging infarct size (g) was decreased in the experimental groups and increased in the control group; 2.4 x 10(7): Delta -2.5 +/- 2.5 g, 2.4 x 10(8): -0.9 +/- 2.71 g, 4.4 x 10(8): -1.6 +/- 5.8 g, and control +3.6 +/- 3.4 g (P = 0.002, P = 0.016, and P = 0.055 compared with control, respectively). There was no effect on ejection fraction or left ventricular volumes. By histology there were no toxic effects of MSC delivery, however, few engrafted MSCs were observed. CONCLUSION: Direct MSC delivery into infarcted myocardium was safe and produced a local but not a functional effect. There was no dose-dependent effect. The effect of MSCs on infarct reduction may result from transient residence and subsequent paracrine effects.
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