Cyclosporin A pre‐incubation attenuates hypoxia/reoxygenation‐induced apoptosis in mesenchymal stem cells

Abstract

Although mesenchymal stem cells (MSCs) are being tested for cardiac repair, the majority of transplanted cells undergo apoptosis in the ischaemic heart because of the effects of ischaemia/reperfusion, poor blood supply and other pro‐apoptotic factors. Several experimental and clinical studies have suggested that cyclosporin A (CsA) treatment reduces apoptosis in human endothelial cells and neurocytes. However, the effect of CsA on the apoptosis in MSCs is still unclear. In this study, we investigated whether CsA could inhibit hypoxia/reoxygenation (H/R)‐induced apoptosis in MSCs. MSCs pre‐incubated with or without CsA were subjected to 6 h of hypoxia followed by 12 h of reoxygenation. Our data showed that pre‐incubation with 0.5–5 µM CsA dose‐dependently protected the MSCs from H/R injury, as evidenced by decreased apoptosis and increased cell viability. CsA inhibited the H/R‐induced translocation of cytochrome c, increased bcl‐2 expression and restored mitochondrial membrane potential. CsA also increased the expression of p‐BAD. We propose that pre‐incubation MSCs with CsA inhibits MSC apoptosis through the mitochondrial and BAD pathway.

• Apoptosis
• BAD cyclosporin A
• mesenchymal stem cell
• mitochondrial function

Acknowledgements

We are indebted to Jun Jiang for expert review of the manuscript and to Ping Chen and Jiang Cao for technical assistance. The work was supported in part through grants from the National Natural Science Foundation of China (no. 30670868) and from the Zhejiang province Natural Science Foundation (no. R206007). Tie‐long Chen and Jian‐an Wang contributed equally to the study.