Human Blood and Cardiac Stem Cells Synergize to Enhance Cardiac Repair When Cotransplanted Into Ischemic Myocardium
| Autor: | Darryl R. Davis, Bin Ye, Bu-Khanh Lam, Erik J. Suuronen, Drew Kuraitis, Duncan J. Stewart, N. Latham, Robyn Jackson, Marc Ruel |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cardiac function curve Cell type Stromal cell Myocardial Ischemia Neovascularization Physiologic Mice SCID Article Mice chemistry.chemical_compound Cell Movement Physiology (medical) Animals Humans Medicine Myocytes Cardiac cardiovascular diseases Myocardial infarction Cells Cultured Aged Peripheral Blood Stem Cell Transplantation business.industry Stem Cells medicine.disease Vascular endothelial growth factor chemistry Heart failure Circulatory system Immunology cardiovascular system Cancer research Female Stem cell Cardiology and Cardiovascular Medicine business Stem Cell Transplantation |
| Zdroj: | Circulation. 128 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.112.000374 |
| Popis: | Background— Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction. The superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the effect of human CACs and CSCs, alone or in combination, on myocardial function in an immunodeficient mouse model of myocardial infarction. Methods and Results— CACs and CSCs were cultured from left atrial appendages and blood samples obtained from patients undergoing clinically indicated heart surgery. CACs expressed a broader cytokine profile than CSCs, with 3 cytokines in common. Coculture of CACs and CSCs further enhanced the production of stromal cell–derived factor-1α and vascular endothelial growth factor ( P ≤0.05). Conditioned media promoted equivalent vascular networks and CAC recruitment with superior effects using cocultured conditioned media. Intramyocardial injection of CACs or CSCs alone improved myocardial function and reduced scar burdens when injected 1 week after myocardial infarction ( P ≤0.05 versus negative controls). Cotransplantation of CACs and CSCs together improved myocardial function and reduced scar burdens to a greater extent than either stem cell therapy alone ( P ≤0.05 versus CAC or CSC injection alone). Conclusions— CACs and CSCs provide unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration, and myocardial repair. Combination therapy with both cell types synergistically improves postinfarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complimentary paracrine signatures that promote revascularization and the growth of new myocardium. |
| Databáze: | OpenAIRE |
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