医学
自愈水凝胶
间质细胞
祖细胞
归巢(生物学)
内皮祖细胞
心肌梗塞
体内
藤黄蛋白C
内科学
干细胞
细胞生物学
化学
生物
免疫组织化学
生态学
生物技术
有机化学
作者
John W. MacArthur,Brendan P. Purcell,Yasuhiro Shudo,Jeffrey Е. Cohen,Alex Fairman,Alen Trubelja,Jay Patel,Philip Hsiao,Eric V. Yang,Kelsey Lloyd,William Hiesinger,Pavan Atluri,Jason A. Burdick,Y. Joseph Woo
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2013-09-10
卷期号:128 (11_suppl_1)
被引量:93
标识
DOI:10.1161/circulationaha.112.000343
摘要
Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction.Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls.We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.
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