| Objective Degradable tissue engineering scaffolds combined with stem cells and neurotrophic factors for the treatment of spinal cord injury are currently the research hotspot and mainstream method in tissue engineering and regenerative medicine.In today’s society,the clinical therapeutic effect of spinal cord injury is still controversial,and the changes in the local microenvironment and the molecular mechanisms of nerve regeneration after spinal cord injury are not yet clear.Effective prevention and mitigation of secondary injury are the key to solving the recovery of motor and sensory functions of the nervous system after spinal cord injury.This project studies on the therapeutic effect of the combination of bone marrow mesenchymal stem cells(BMSC),neurotrophic factor 3(NT-3)and hydrogels on spinal cord injury,assesses its safety and promotes the successful transformation from basic research on neural regeneration and repair after spinal cord injury to clinical research.Methods Firstly,SD rat BMSCs were cultured and genetically modified to over express NT-3 and to be verified,and hydrogels were made and loaded with cells.The experimental rats were divided into Sham operation control group(Sham),spinal cord injury model group(SCI model),BMSC+NT-3 group,BMSC+hydrogels group,BMSC+hydrogels+GFP group and BMSC+hydrogels+NT-3 group,a total of 6 groups,8 rats in each group.Then,the model of acute incomplete spinal cord injury in SD rats was established and treated respectively.Finally,the combined therapeutic effect for spinal cord injury was tested by postoperative motor behavior(Basso Beatlie Bresnahan,BBB score)and pathology.Results BBB scores of SD rats in each combined treatment group increased to varying degrees,and the treatment effect of the BMSC+NT-3+hydrogels group was the most obvious.Immunohistochemical test showed that the number of neurons and nerve fibers in each combined treatment group increased to varying degrees,and the number of astrocytes was small.In the treatment group,rats in the BMSC+NT-3+hydrogels group had the largest number of neurons and nerve fibers,and the smallest number of astrocytes.The neurons and nerve fibers in BMSC+hydrogels+NT-3 group increased significantly,astrocytes decreased,and glial scars decreased,compared with that in BMSC+NT-3 group.Compared with that in BMSC+hydrogels+GFP group,the neurons and nerve fibers increased in BMSC+hydrogels+NT-3 group,while the proliferation of glial scars formed by astrocytes decreased.The neurons in BMSC+hydrogels+GFP group decreased to a certain extent and astrocytes increased,compared with that in BMSC+hydrogels group,and there was no statistical difference in the number of nerve fibers between these two groups.HE staining showed that the experimental rats in each group had normal morphology of some visceral organs,such as heart,brain,liver and kidney,suggesting that the combined treatment of BMSC,NT-3 and hydrogels for spinal cord injury is safe.Conclusions The therapeutic effect of the combination of bone marrow mesenchymal stem cells,neurotrophic factor 3 and hydrogels on spinal cord injury is better than that of two parts.Bone marrow mesenchymal stem cells,neurotrophic factor-3 and hydrogel scaffolds promote each other in the treatment of spinal cord injury.Joint transplantation is applied to acute incomplete spinal cord injury model rats,which can improve the model rats’ hindlimb application behavior ability;it can promote neurons and nerve fibers to regenerate and repair,and can inhibit the formation of glial scars in injured segments.This study suggests that the preparation of a more effective and injectable cell+factor+scaffold composite material can provide new ideas for the treatment of nerve repair and regeneration of spinal cord injury. |
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