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Sildenafil increases the efficacy of adipose derived stem cell transplantation following myocardial infarction
Author(s) -
Hoke Nicholas,
Salloum Fadi,
Woolbright Benjamin,
Das Anindita,
Kukreja Rakesh
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.679.2
Background Enhancing the viability of stem cells injected into ischemic microenvironments by novel preconditioning strategies is critical for improving cellular therapy. We hypothesized that preconditioning of adipose derived stem cells (ASCs) with sildenafil (SIL) would improve survival after ischemia/reoxygenation and post‐ischemic function following myocardial transplantation. Methods and Results ASCs were preconditioned with 10 μM SIL for 2 hours prior to simulated ischemia (SI) and reoxygenation (RO). SIL preconditioning attenuated necrosis, LDH release, and apoptosis as compared to SI/RO control. Additionally, CD‐1 mice underwent permanent occlusion of left coronary artery. Control or SIL preconditioned ASCs were directly injected into myocardium. Echocardiography results 4 weeks after surgery showed reduced LV dilatation and preserved ejection fraction with SIL preconditioned ASCs. Furthermore, SIL preconditioned ASC group had significantly reduced fibrosis (7.1± 0.3% vs. 13.6±0.8%), increased vascular density (8.3±0.7 vs. 4.5±0.3) and reduced resident myocyte apoptosis as compared to the group receiving non‐preconditioned ASCs. Conclusion SIL may provide a novel strategy to enhance therapeutic potential of ASCs as indicated by reduced fibrosis, cardiomyocytes apoptosis, improved vascular density and cardiac function following ischemia.