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

¹ Georgia Institute of Technology, Atlanta, GA, 30332, USA; Emory University, Atlanta, GA, 30322 USA
² Atlanta Veteran Affairs Medical Center, Decatur, GA, 30033, USA; Emory University, Atlanta, GA, 30322 USA
³ Georgia Institute of Technology, Atlanta, GA, 30332, USA

^* To whom correspondence should be addressed. E-mail: sdudley{at}emory.edu.

	Abstract

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 CDF rats, and patches with or without cells were secured to hearts with fibrin sealant. After patch formation, hMSC retained a viability of >90% over five days in culture. In addition, >75% of hMSC maintained a high degree of potency prior to patch implantation. After four days in culture, patches were applied to the epicardial surface of the infarct area and resulted in 23 ± 4% engraftment of hMSC at one week (n=6). Patch application resulted in a reduction in LV interior diameter at systole, increased anterior wall thickness and a 30% increase in fractional shortening. Despite this improvement in myocardial remodeling, hMSC were not detectable at 4 weeks after patch application, implying improvement did not require long-term cell engraftment. Patches devoid of progenitor cells showed no improvement in remodeling. In conclusion, pluripotent hMSC can be efficiently delivered to a site of myocardial injury and such delivery results in improved myocardial remodeling after infarction.

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