Atluri, PavanMiller, Jordan S.Emery, Robert J.Hung, GeorgeTrubelja, AlenCohen, Jeffrey E.Lloyd, KelseyHan, JasonGaffey, Ann C.MacArthur, John W.Chen, Christopher S.Woo, Y. Joseph2015-10-282015-10-282014Atluri, Pavan, Miller, Jordan S., Emery, Robert J., et al.. "Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function." <i>The Journal of Thoracic and Cardiovascular Surgery,</i> 148, no. 3 (2014) Elsevier: 1090-1098. http://dx.doi.org/10.1016/j.jtcvs.2014.06.038.https://hdl.handle.net/1911/81938Objectives: Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. Methods: Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein+ endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 106 endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein+ rodents. Results: Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein+ endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. Conclusions: We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.engThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.Journal articlebioengineeringhydrogelEndothelial Progenitor Cellvasculogenesisischemic cardiomyopathyhttp://dx.doi.org/10.1016/j.jtcvs.2014.06.038