Bone Marrow Stem Cells Contribute to Cardioprotection in the Late Phase of Ischemic Preconditioning

Ischemic preconditioning (IPC) is a well-known innate phenomenon, in which brief exposure to sublethal ischemia protects organs from subsequent isch- emia/reperfusion (I/R) injury. The protective effects after IPC occur in two distinct phases: an early phase and a late phase. However, the exact protective mechanism of IPC is not fully understood, especially in the late phase. Based on increasing evidence that bone marrow stem cells (BMSCs) can repair the injured heart, we investigated whether they also play a role in protecting the heart against I/R injury in the late phase of IPC. We observed an increase in cardioprotective factors in the serum in the early phase, but an increase in BMSCs in the circulating blood in the late phase af- ter remote IPC. Using a heart I/R injury model, we demonstrated that the mobilized BMSCs were recruited into the injured heart and contributed to cardioprotection, especially in the late phase of IPC. Our results indicate that IPC enhances the mobi- lization and recruitment of BMSCs in the late phase to protect the heart against I/R injury.