Abstract 18801: Intracardiac Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating the Release of Endothelial Progenitor Cells
Background: While mesenchymal stem cells (MSCs) exert immunomodulatory and antifibrotic effects in humans, preclinical studies also indicate that these cells can interact with host precursor cells, so as to promote tissue and organ function renewal. In human heart failure, this effect could have both cardiac and systemic vascular implications. The mechanism(s) of action by which MSCs exert favorable cardiovascular effects in human heart failure remain controversial. As heart failure is associated with endothelial dysfunction, impaired neovascularization, and diminished endothelial progenitor cell (EPC) abundance, we tested the hypothesis that MSCs simulate circulating EPCs and flow-mediated vasodilation in patients with heart failure due to dilated cardiomyopathy.
Methods: We quantified EPC-colony forming units (EPC-CFUs) from peripheral blood in patients (n=16) and healthy controls (n=6), and compared these to flow-mediated vasodilation (FMD) before and 3-months after intracardiac injection of MSCs. Patients were randomly assigned to receive either autologous (n=7) or allogeneic (n=9) MSCs.
Results: Patients with DCM have significantly reduced EPC-CFUs compared to healthy controls, 4±3 colonies vs. 43±10, P<0.0001. In addition, patients exhibited impaired FMD%, 5.9±3.6% compared to controls, 11.4±3.2% (P=0.003), and this effect was strongly correlated with EPC-CFUs (P<0.0001). Three months after treatment, allogeneic but not autologous MSCs significantly improved endothelial function as evident by both EPC-CFUs (Δ10±5 colonies vs. Δ1±3 colonies respectively, P<0.0001) and FMD% (Δ 3.4±2.9% vs Δ –0.46±3.0%, P=0.003). Furthermore, a strong association between FMD% and EPC-CFUs remained after treatment (P=0.004).
Conclusion: These findings illustrate that patients with DCM and endothelial dysfunction experience significantly improved endothelial function, at least in part due to stimulating endogenous EPCs, following allogeneic but not autologous MSCs administration. These findings have important clinical and biological implications for the use of MSCs in human heart failure and other disorders associated with endothelial dysfunction.
Author Disclosures: C. Premer: None. A. Blum: None. M. Bellio: None. I.H. Schulman: None. J. Sierra: None. C. Delgado: None. B. Hurwitz: None. D. Difede: None. M. Parker: None. P. Gonzalez: None. J.M. Hare: Employment; Modest; Vestion. Ownership Interest; Modest; Biscayne. Ownership Interest; Significant; Vestion Inc.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.