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TRANSLATIONAL AND CLINICAL RESEARCH

A Tissue Engineering Approach to Progenitor Cell Delivery Results in Significant Cell Engraftment and Improved Myocardial Remodeling

^aDepartment of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA;
^bDivision of Cardiology, Atlanta Veterans Affairs Medical Center, Decatur, Georgia, USA;
^cDivision of Cardiology, Emory University, Atlanta, Georgia, USA

Key Words. Tissue engineering • Mesenchymal stem cell transplantation • Myocardial infarction • Ventricular remodeling

Correspondence: Samuel C. Dudley, Jr., M.D., Ph.D., Division of Cardiology, Emory University/Veterans Affairs Medical Center, 1670 Clairmont Road (111B), Decatur, Georgia 30322, USA. Telephone: 404-329-4626; Fax: 404-329-2211; e-mail: sdudley{at}emory.edu

Received February 19, 2007; accepted for publication May 17, 2007.
First published online in STEM CELLS EXPRESS   May 24, 2007.



Cell replacement therapy has become an attractive solution for myocardial repair. Typical cell delivery techniques, however, suffer from poor cell engraftment and inhomogeneous cell distributions. Therefore, we assessed the hypothesis that an epicardially applied, tissue-engineered cardiac patch containing progenitor cells would result in enhanced exogenous cell engraftment. Human mesenchymal stem cells (hMSCs) were embedded into a rat tail type I collagen matrix to form the cardiac patch. Myocardial infarction was induced by left anterior descending coronary artery ligation in immunocompetent male cesarean-derived fischer rats, and patches with or without cells were secured to hearts with fibrin sealant. After patch formation, hMSCs retained a viability of >90% over 5 days in culture. In addition, >75% of hMSCs maintained a high degree of potency prior to patch implantation. After 4 days in culture, patches were applied to the epicardial surface of the infarct area and resulted in 23% ± 4% engraftment of hMSCs at 1 week (n = 6). Patch application resulted in a reduction in left ventricle interior diameter at systole, increased anterior wall thickness, and a 30% increase in fractional shortening. Despite this improvement in myocardial remodeling, hMSCs were not detectable at 4 weeks after patch application, implying that improvement did not require long-term cell engraftment. Patches devoid of progenitor cells showed no improvement in remodeling. In conclusion, pluripotent hMSCs can be efficiently delivered to a site of myocardial injury using an epicardial cardiac patch, and such delivery results in improved myocardial remodeling after infarction.

Disclosure of potential conflicts of interest is found at the end of this article.

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				S. C. Dudley Jr and D. Simpson An Imperfect Syllogism: Granulocyte Colony-Stimulating Factor Mobilization and Cardiac Regeneration J. Am. Coll. Cardiol., April 15, 2008; 51(15): 1438 - 1439. [Full Text] [PDF]