Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function

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dc.citation.firstpage1090en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitleThe Journal of Thoracic and Cardiovascular Surgeryen_US
dc.citation.lastpage1098en_US
dc.citation.volumeNumber148en_US
dc.contributor.authorAtluri, Pavanen_US
dc.contributor.authorMiller, Jordan S.en_US
dc.contributor.authorEmery, Robert J.en_US
dc.contributor.authorHung, Georgeen_US
dc.contributor.authorTrubelja, Alenen_US
dc.contributor.authorCohen, Jeffrey E.en_US
dc.contributor.authorLloyd, Kelseyen_US
dc.contributor.authorHan, Jasonen_US
dc.contributor.authorGaffey, Ann C.en_US
dc.contributor.authorMacArthur, John W.en_US
dc.contributor.authorChen, Christopher S.en_US
dc.contributor.authorWoo, Y. Josephen_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2015-10-28T19:04:03Zen_US
dc.date.available2015-10-28T19:04:03Zen_US
dc.date.issued2014en_US
dc.description.abstractObjectives: 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.en_US
dc.identifier.citationAtluri, 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.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.jtcvs.2014.06.038en_US
dc.identifier.urihttps://hdl.handle.net/1911/81938en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordbioengineeringen_US
dc.subject.keywordhydrogelen_US
dc.subject.keywordEndothelial Progenitor Cellen_US
dc.subject.keywordvasculogenesisen_US
dc.subject.keywordischemic cardiomyopathyen_US
dc.titleTissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Functionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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