Ischemic Pre-Conditioning Enhances the Mobilization and Recruitment of Bone Marrow Stem Cells to Protect Against Ischemia/Reperfusion Injury in the Late Phase

Objectives: The aim of this study was to investigate whether the mobilization and recruitment of bone marrow stem cells (BMSCs) contribute to cardioprotection in the late phase after ischemic pre-conditioning (IPC). Background: IPC is an innate phenomenon in which brief exposure to sublethal ischemia provides tissue protection from subsequent ischemia/reperfusion (I/R) injury. A delayed cardioprotection also occurs after IPC, but the precise mechanism is unclear. Methods: IPC was created with 4 cycles of 5-min occlusion and reperfusion of the abdominal aorta in mice. Heart I/R injury was induced by occluding the left anterior descending artery for 30 min immediately (early phase) or 24 h (late phase) after IPC. Results: Serum vascular endothelial growth factor and stromal cell-derived factor-1α levels were increased significantly 1 and 3 h after IPC, but CD34+ and CD34+/flk-1+ stem cells in the peripheral blood were increased significantly 12 and 24 h after IPC (p < 0.05). Compared with the control treatment, both the early and late phases of IPC protected the heart against I/R injury. However, the recruitment of BMSCs was significantly greater in the heart when I/R injury was induced in late phase than in the early phase of IPC (p < 0.01). Interestingly, the blockade of the recruitment of BMSCs significantly attenuated the cardioprotective effect of IPC in the late phase (p < 0.01) but did not change in the early phase. Conclusions: Cardioprotection was observed in the early and late phases of IPC; however, the enhanced mobilization and recruitment of BMSCs played an important role in the late phase of IPC.