Objective Cell transplantation was supposed to be a therapeutic strategy of myocardial infarction, but the problem was that most of the transplanted cells died at the early stage of transplantation. We hypothesised that over-activation of induced nitric oxide synthase (iNOS) may play an important role in the death of transplanted cells. In this experiment, we investigated the effect of iNOS selective inhibitor on the survival of transplanted bone marrow stem cells (BMSCs).
Methods BMSCs were isolated from the male SD rats. Female SD rats were subjected to myocardial infarction by ligation of left anterior descending artery. BMSCs at 1.2×106 were injected into the central zone of the infarct region at 1 h after ligation. BMSCs were monitored by labelled BrdU or Hoechst33342. A Sry gene sequence of Y chromatosome in male rats was analysed by real-time PCR for the quantification of the survived BMSCs in host myocardium.
Results The cultured BMSCs showed a homogenous pattern with CD44+/CD34-. Accumulation of BMSCs labelled with Hoechst33342 or BrdU was noted in infarct area of the host heart. Myocardial infarction induced a significant iNOS expression with its peak expression on day 3 and lasting for 14 days. The survival rates of engrafted BMSCs by real-time PCR were 7.88%, 7.82% and 8.73% at 1 week, 3 weeks and 6 weeks after transplantation respectively. iNOS selective inhibitor 1400 W contributed to 32% increase In the survival rate of the transplanted BMSCs. Migration of transplanted BMSCs to the margin area of infarct region was observed in Hoechst33342 or BrdU labelled BMSCs.
Conclusion 1 week after transplantation, the survival rate of BMSCs was as low as around 8% and there was no progressive decrease from 3 to 6 weeks post transplantation. iNOS selective inhibitor 1400 W may result in 32% increase in the survival rate of transplanted BMSCs.
- Myocardial infarction
- induced nitric oxide synthase inhibitor