Allogeneic Mesenchymal Stem Cells Restore Cardiac Function In Chronic Ischemic Cardiomyopathy Via Trilineage Differentiating Capacity

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Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity
falseQuevedo, Henry C; Hatzistergos, Konstantinos E; Oskouei,Behzad N
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; Feigenbaum, Gary S; Rodriguez, Jose E; et al..Proceedings of the National Academy of Sciences of the United States of America106. 33 (Aug 18, 2009):14022.
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The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesisthat MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine receivedcatheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fatewas determined by co-localization of Y-chromosome (Ypos) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated intocardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and a-sarcomeric actin. In addition, Ypos MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing tolarge and small vessel formation. Infarct size was reduced from 19.3 ± 1.7% to 13.9 ± 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 ± 1.7% to 41.3 ± 2.7% (P < 0.05) in MSCbut not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment...
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