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F8. Stromal cell-derived factor-1α gene therapy improves endothelial progenitor cells mobilization, myocardial neovascularization and cardiac function in chronic myocardial infarction
Yao Liang Tang, Kepin Qian, Lepin Shen, Vinay Badhwar, M. Ian Phillips; St. Petersburg, TampaFL

Objective: Cell therapy with endothelial progenitor cells (EPCs) is a novel strategy for improving neovascularization and cardiac function in ischemic heart disease. Stromal cell derived factor-1α (SDF-1α) is a CXC-type chemokine, which play important roles in mobilizing circulating EPCs. However, endogenous SDF-1 expression after MI is low and transient, which can not mobilize enough EPCs for therapeutic neovascularization. We therefore studied the effect of SDF-1α gene therapy on EPCs mobilization, myocardial neovascularization, left ventricular (LV) remodeling and function.
Methods: Adult mice with extensive anterior MI were randomized to intramyocardial injection with pCMV-SDF-1α plasmid or saline (n=20/grop) at 2 weeks after MI. Labeled EPCs (6x10⁵) were intravenously injected 3 days after plasmid administration to test the direction of EPCs mobilization.
Results: We show that increasing the number of EPCs trafficking to the peri-infarct region of SDF-1α overexpression and results in neovascularization with development of progressively small to larger-sized capillaries at 2 weeks after treatment. LV dysfunction and interstitial fibrosis were markedly attenuated 2 weeks after gene therapy, systolic function, assessed by left ventricular develop pressure (LVDP), was significant improved in SDF-1α treated hearts compared with saline hearts (94.9±2.3 vs 83.1±1.9 mmHg, P=0.002,n=6).
Conclusions: These findings suggest that SDF-1α gene therapy improve EPCs mobilization, induce neovascularization, prevent myocardial remodeling and enhance cardiac function after MI. Mobilized EPCs mediates beneficial effects of SDF-1α treatment after MI.

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