通过预处理短暂诱导缺氧适应不能提高脊髓损伤后雪旺细胞移植的存活率

Temporary induction of hypoxic adaptations by preconditioning fails to enhance Schwann cell transplant survival after spinal cord injury

缺氧预处理在多种损伤和疾病模型中具有保护作用,但它是否对移植到脊髓损伤(SCI)部位的细胞有益在很大程度上尚待探索。本研究分析了缺氧相关的预处理是否能保护移植到挫伤的大鼠胸髓中的雪旺细胞(SC)。雪旺细胞在移植前通过暴露于低氧(1%O2)或药物制剂(去铁胺或adaptaquin)诱导缺氧预处理。所有预处理方法均诱导缺氧适应,包括HIF-1α及其靶基因的表达增加。然而这些适应是短暂的,并在移植后24 h内消失。药理学预处理减弱了脊髓氧化应激,并增强了移植血管形成,但它并没有改善移植细胞的存活或感觉/运动功能的恢复。总之,这些实验结果表明,与缺氧相关的预处理在改善脊髓损伤后移植雪旺细胞的细胞存活或功能方面是无效的。本研究还揭示了在细胞移植疗法中由预处理引起的缺氧相关适应的益处并不普遍。

Hypoxic preconditioning is protective in multiple models of injury and disease, but whether it is beneficial for cells transplanted into sites of spinal cord injury(SCI) is largely unexplored. In this study, we analyzed whether hypoxia-related preconditioning protected Schwann cells(SCs) transplanted into the contused thoracic rat spinal cord.Hypoxic preconditioning was induced in SCs prior to transplantation by exposure to either low oxygen(1% O2) or pharmacological agents(deferoxamine or adaptaquin). All preconditioning approaches induced hypoxic adaptations,including increased expression of HIF-1 α and its target genes. These adaptations, however, were transient and resolved within 24 h of transplantation. Pharmacological preconditioning attenuated spinal cord oxidative stress and enhanced transplant vascularization, but it did not improve either transplanted cell survival or recovery of sensory or motor function. Together, these experiments show that hypoxia-related preconditioning is ineffective at augmenting either cell survival or the functional outcomes of SC-SCI transplants. They also reveal that the benefits of hypoxia-related adaptations induced by preconditioning for cell transplant therapies are not universal.