在体缺血预处理增强骨髓基质细胞移植对脊髓缺血再灌注损伤的保护作用及机制研究

Spinal cord ischemia is a well-recognized complication of acute aortic occlusion for resuscitation for the purposes of elective or emergency aortic reconstruction. Bone marrow stromal cells (BMSCs) transplantation has a protective effect on ischemia-reperfusion spinal cord, but most of the cells die after transplantation, which severely limits its repairment. The recruitment of stem cells migrating to the injuried tissue is the key to success in the treatment of cell transplantation. Previous studies were concentrated on preconditioning BMSCs in vitro to improve their anti-ischemia tolerance. In this project, we firstly applied ischemic preconditioning, a clinically simple, safe and viable operation to pretreat spinal cord directly before ischemia-reperfusion injury and transplantation of BMSCs in rats. According to our hypothesis, ischemic preconditioning protects the transplanted cells and improves the migration, differentiation and paracrine function, further enhances the protective effects of BMSCs. On this basis, we culture BMSCs in spinal cord homogenate supernatant performed with ischemic preconditioning in vitro and investigate the role of HIF-1α-SDF-1-CXCR4/CXCR7 signaling axis on improvement of migration, survival and function of BMSCs induced by ischemic preconditioning. This project not only provides a new high-efficient program for BMSCs transplantation in the treatment of spinal cord ischemic injury, also brings a new idea for clinical and translational applications of stem cells in other ischemia-reperfusion injuried organs.

脊髓缺血再灌注损伤是临床胸腹主动脉瘤手术最严重的并发症之一，可引起截瘫，是现代医学中急待攻克的难题。目前骨髓基质细胞移植治疗脊髓损伤备受关注，但是移植后干细胞死亡严重限制其修复作用，招募干细胞迁移到受损组织也是细胞移植治疗成败的关键。既往研究都集中在体外预处理干细胞提高其抗缺血缺氧耐受力，本项目首次提出应用临床上操作简单、安全可行的缺血预处理方法，在大鼠缺血再灌注损伤前直接预处理脊髓组织，期望保护移植的干细胞，并促进其迁移、分化和旁分泌功能，进而增强骨髓基质细胞的脊髓保护作用。并通过体外实验在缺血预处理脊髓组织匀浆培养液中培养骨髓基质细胞，探讨HIF-1α-SDF-1-CXCR4/CXCR7信号轴在缺血预处理增强移植骨髓基质细胞迁移、存活和功能中的作用。本项目不仅为优化骨髓基质细胞移植治疗脊髓缺血再灌注损伤提供高效能的方案，也为干细胞在其他器官缺血再灌注损伤中的临床和转化应用提供新思路。

脊髓缺血再灌注损伤是临床胸腹主动脉瘤手术最严重的并发症之一，可引起截瘫，是现代医学中急待攻克的难题。目前骨髓基质细胞移植治疗脊髓损伤备受关注，但是移植后干细胞死亡严重限制其修复作用，招募干细胞迁移到受损组织也是细胞移植治疗成败的关键。既往研究都集中在体外预处理干细胞提高其抗缺血缺氧耐受力，本项目首次提出应用临床上操作简单、安全可行的缺血预处理方法，在大鼠缺血再灌注损伤前直接缺血预处理脊髓组织，保护移植的干细胞，并促进其迁移、存活、分化和旁分泌功能，进而增强骨髓基质细胞的脊髓保护作用。HIF-1α-SDF-1-CXCR4/CXCR7信号轴参与其中的保护机制。本项目不仅为优化骨髓基质细胞移植治疗脊髓缺血再灌注损伤提供高效能的方案，也为干细胞在其他器官缺血再灌注损伤中的临床和转化应用提供新思路。