title: A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling.
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 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.
authors.affiliation: Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Tai-Hwang Michael
authors.initials: TH
authors.lastname: Fan
authors.forename: Robert
authors.initials: R
authors.lastname: Nerem
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Dudley
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D016896:Treatment Outcome; D020257:Ventricular Remodeling
chemical_list: D000199:Actins; C498862:Acta2 protein, rat