Stromal Cell-Derived Factor-1α Activation of Tissue-Engineered Endothelial Progenitor Cell Matrix Enhances Ventricular Function After Myocardial Infarction by Inducing Neovasculogenesis
| Autor: | Ryan C. McCormick, Jeffrey R. Muenzer, Nicole A. Marotta, Pavan Atluri, John R. Frederick, Jeffrey E. Cohen, Y. Joseph Woo, Ah-Young Kim, J. Raymond Fitzpatrick, Maximilian J. Smith, David A. Harris, William Hiesinger |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Pathology Angiogenesis Myocardial Infarction Neovascularization Physiologic Endothelial progenitor cell Article Extracellular matrix chemistry.chemical_compound Vasculogenesis Physiology (medical) Ventricular Dysfunction Animals Humans Medicine Myocytes Cardiac Vitronectin Myocardial infarction Ventricular remodeling Cells Cultured Tissue Engineering business.industry Stem Cells Endothelial Cells medicine.disease Chemokine CXCL12 Extracellular Matrix Rats Surgery Vascular endothelial growth factor Endothelial stem cell Disease Models Animal chemistry Rats Inbred Lew cardiovascular system Collagen Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 122 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.109.930404 |
| Popis: | Background— Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPCs) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that implantation of a tissue-engineered extracellular matrix (ECM) scaffold seeded with EPCs primed with SDF could induce borderzone neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after myocardial infarction. Methods and Results— Lewis rats (n=82) underwent left anterior descending artery ligation to induce myocardial infarction. EPCs were isolated, characterized, and cultured on a vitronectin/collagen scaffold and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular wall, which included the region of ischemia. Control animals received sutures but no EPCM. Additional groups underwent application of the ECM alone, ECM primed with SDF (ECM+SDF), and ECM seeded with EPCs but not primed with SDF (ECM+SDF). At 4 weeks, borderzone myocardial tissue demonstrated increased levels of vascular endothelial growth factor in the EPCM group. When compared to controls, Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 versus 6.2 vessels/high-powered field; P P =0.04). Comparisons to additional groups also showed a significantly improved vasculogenic response in the EPCM group. Ventricular geometry and scar fraction assessed by digital planimetric analysis of sectioned hearts exhibited significantly preserved left ventricular internal diameter (9.7 mm versus 8.6 mm; P =0.005) and decreased infarct scar formation expressed as percent of total section area (16% versus 7%; P =0.002) when compared with all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure-volume conductance, and Doppler flow. Conclusions— Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after myocardial infarction. |
| Databáze: | OpenAIRE |
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