Endothelial Function in Heart Failure Patients receiving Mesenchymal Stem Cell Therapy

  • Premer, Courtney (PI)

Project Details

Description

Heart failure (HF) is one of the leading causes of morbidity and mortality in the United States. Recent clinical trials in HF patients with ischemic cardiomyopathy illustrate that mesenchymal stem cell (MSC) therapy improves cardiac function. While MSCs exert immunomodulatory and antifibrotic effects in humans, the mechanism(s) of action remain controversial. HF is associated with endothelial dysfunction and diminished endothelial progenitor cell (EPC) abundance. The therapeutic effects of MSCs are thought to be due to a combination of their ability to self-renew, differentiate into mesoderm and nonmesoderm-derived tissues, and secrete paracrine factors. Preliminary data indicates that MSC therapy greatly improves endothelial function via an increase in endothelial progenitor cell (EPCs) colonies and an improvement in flow-mediated vasodilation percent (FMD %). Thus, my long-term goal is to elucidate whether targeting endothelial function via MSC therapy ameliorates cardiovascular function in HF patients. My central hypothesis is: MSCs secrete endothelial-promoting factors in a donor-dependent manner that influence circulating EPCs, therefore affecting endothelial function in HF patients. The aims of my proposal are: 1) to test the hypothesis that MSCs improve systemic endothelial function in heart failure patients by stimulating EPC function and increasing FMD%, and 2) to test the hypothesis that MSCs improve endothelial function through increased nitric oxide bioavailability, stimulation of the angiogenic capacity of endothelial cells and upregulation of endothelial gene expression in EPCs, and suppression of circulating inflammatory cytokines. (AHA Program: Predoctoral Fellowship)

StatusFinished
Effective start/end date1/07/153/02/17

Funding

  • American Heart Association: $52,000.00

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