神经祖细胞,脊髓损伤 z-bo 2020-09-30 320

　　Neural progenitor cells (NPC) are a potential treatment method for repairing and regenerating neurons after spinal cord injury. However, after NPC is transplanted into rodents, the harmful microenvironment of the damaged spinal cord leads to limited recovery.

　　In a new study, researchers at the University of Toronto and other research institutions in Canada found that in the spinal cord microenvironment of rodents, notch activation caused by spinal cord injury would be destined to be transplanted to their NPCs. It has been found that the cells are biased towards stellate cells. In the process of screening for potential clinically relevant factors that regulate Notch signaling, they identified glial cell-derived neurotrophic factor (GDNF). GDNF mediates the expression of DLK1 (delta-like1homolog) and attenuates Notch signal, which has nothing to do with the effect of GDNF on cell survival. When transplanted into a rodent cervical spinal cord injury model, human induced pluripotent stem cell-derived NPC (hipsC-NPC) expressing GDNF differentiated into neurons instead of control cells.

　　In addition, the expression of GDNF promotes the protection of endogenous tissues and enhances the electrical integration of transplanted cells, thereby jointly improving the recovery of neurobehavior. In the hip C-NPC expressing GDNF, CRISPR-induced DLK1 gene knockout may attenuate the effect on functional recovery, confirming that this effect is partly mediated by DLK1 expression. These results represent a mechanism-driven optimization of hiPSC-NPC treatment that redirects transplanted hipsC-NPC to the fate of neurons and enhances their integration. In addition, they also suggested that adjusting the damaged spinal cord microenvironment can improve the functional recovery of NPC after transplantation.