Exercise and Stem Cell Engraftment in the Heart Following Myocardial Infarction

描述（由申请人提供）：随着心血管生物学进入心脏病干细胞/祖细胞治疗时代，了解运动如何影响祖细胞生物学和治疗非常重要。本文提出的实验将首次测试运动是否能“预先”梗死后心肌以更有效地保留外源注入的祖细胞。虽然迄今为止的研究表明，细胞治疗可以改善心肌梗死患者的左心室功能，但低祖细胞植入率限制了治疗的效果。改善先天性心肌表型以促进祖细胞归巢、植入和增殖，可能会增加细胞治疗的临床潜力。有氧运动是一种特殊的干预措施

DESCRIPTION (provided by applicant): As cardiovascular biology enters the era of stem/progenitor cell therapy for heart disease, it is important to understand how exercise impacts progenitor cell biology and therapy. Experiments outlined in this proposal will for the first time test whether exercise can "precondition" the post-infarcted myocardium to more effectively retain exogenously-infused progenitor cells. While research to date has shown that cell-based therapy can improve left ventricular function in myocardial infarction, low progenitor cell engraftment rates have limited the efficacy of the treatment. Improving the innate myocardial phenotype for progenitor cell homing, engraftment, and proliferation will likely augment the clinical potential of cell-based therapy. Aerobic exercise is one specific intervention known to improve myocardial phenotype. A host of studies have shown that exercise improves cardiac ischemia-reperfusion tolerance, decreases apoptosis, augments myocardial blood flow, and alters various hormonal and metabolic cardiomyocyte signaling pathways. The novel experiments outlined in this proposal are designed to test the specific hypothesis that acute aerobic exercise improves homing and engraftment of exogenously-infused bone marrow-derived progenitor cells (BMC's) to the infarcted C57BL/6J mouse heart. We will also determine to what extent exercise augments new cardiomyocyte formation from exogenous and endogenous cell pools. Feasibility studies from our laboratory support these hypotheses, and results from the proposed studies will provide crucial translational information regarding the required "dose" of exercise necessary to optimize myocardial BMC retention and form new cardiomyocytes. Results from these experiments will establish the basis for subsequent experiments in transgenic mice and then in humans.