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.

Public Health Relevance

Aerobic exercise induces a host of beneficial effects on the heart and may be able to improve the engraftment of stem cells, thereby improving the therapeutic efficacy of stem cell interventions for heart disease. Aerobic exercise may also potentiate heart cell formation. Studies outlined in this proposal will provide crucial information regarding the required dose of acute exercise necessary to optimize stem cell therapy in myocardial infarction and will provide the basis for subsequent experiments in humans.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL113777-01A1
Application #
8435690
Study Section
Cardiac Contractility, Hypertrophy, and Failure Study Section (CCHF)
Program Officer
Wong, Renee P
Project Start
2013-02-15
Project End
2015-01-31
Budget Start
2013-02-15
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$200,000
Indirect Cost
$75,000
Name
University of Pennsylvania
Department
Other Health Professions
Type
Schools of Nursing
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104