Circulation. 2005;111:150-156
Published online before print January 10, 2005, doi: 10.1161/01.CIR.0000151812.86142.45
Published online before print January 10, 2005, doi: 10.1161/01.CIR.0000151812.86142.45
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(Circulation. 2005;111:150-156.)
© 2005 American Heart Association, Inc.
Coronary Heart Disease |
Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model
From the Texas Heart Institute at St Luke’s Episcopal Hospital, Houston, Tex; and Osiris Therapeutics, Inc (B.J.M.), Baltimore, Md.
Correspondence to Emerson C. Perin, MD, PhD, St Luke’s Episcopal Hospital, 6624 Fannin, Suite 2220, Houston, TX 77030. E-mail eperin{at}crescentb.net
Received May 28, 2004; revision received July 23, 2004; accepted August 12, 2004.
Background— Bone marrow–derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking.
Methods and Results— Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x106 MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes.
Conclusions— In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.
Key Words: cells • heart failure • ischemia • revascularization
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