Overexpression of Inducible Nitric Oxide Synthase Impairs the Survival of Bone marrow Stem Cells Transplanted into Rat Infarcted Myocardium

Aims: Inducible nitric oxide synthase (iNOS) over-expression is considered critical to the death of transplanted cells in infarcted myocardium. The present study was to investigate the effect of iNOS on the survival of transplanted bone marrow mesenchymal stem cells (BMSCs) in infarcted myocardium. Main methods and key findings: Male rat BMSCs were injected into the infarct region of female rat hearts at 1 hour (H1, group A), day 3 (D3, group B), and day 7 (D7, group C) after coronary artery ligation, and harvested on D7 after transplantation. Myocardial iNOS expression was significantly increased shortly after coronary ligation with its peak on D3, and returned to baseline at D7. The cell survival rates were 62%, 2.1%, and 83% in group A, B, and C, respectively, one week after transplantation as assessed by detecting the Y-chromosome sty sequence in the infarct region. There was no significant difference in the survival rates between D7 and week 6 after cell transplantation in group A. Treating the animals in group B with the selective iNOS inhibitor 1400W significantly increased the survival rate (from 1.8% to 4.2%). Apoptosis level of the transplanted cells was also significantly reduced with 1400W treatment in group B. Significance: BMSC transplantation on H1 and D7 after coronary ligation might be the optimal time for cell survival. The loss of transplanted BMSCs in the infarcted myocardium was partially due to increased apoptosis and iNOS overexpression. Selective iNOS inhibition early in myocardial infarction may increase the cell viability. (C) 2014 Elsevier Inc All rights reserved.