Research On The Changes Of Gene Expression Profiling After Umbilical Cord Blood Neural Stem Eells (UCBNSCs) Treat On Spinal Cord Injury And The Preliminary Appiication Of UCBNSCs In Clinic

Objective Using umbilical cord blood neural stem cells(UCBNSCs) transplantationto treat spinal cord injury (SCI)in rats and assess the hind limbs function,then identifydifferentially expressed genes between the experimental group and PBS control groupby gene chips,analysis the relationship between the genes and functional recovery ofthe spinal cord to lay foundation for the gene therapy of spinal cord injury.To explorethe possibility and clinical effect of UCBNSCs transplantation for patients withobsolete spinal cord injury.Method1.60healthy female SD rats were randomly divided into sham-operationgroup (n=10), PBS injection control group (n=20), UCBNSCs transplantationgroup (n=30). Only open the T9-11vertebral plate in control group with microscope，the spinal cord of another two groups need to be cut off after openning the T9-11vertebral plate to make the model of rats spinal cord transection. UCBNSCstransplantation operation is took through ventricular puncture(1x107/L cellsuspension10ul)1week later.4SD rats of UCBNSCs group executed aftertransplantation respectively on2nd week,4th week,8th week, Immunohistochemicalstaining is took to see the survival situation of UCBNSCs and the differentiation on2th week in the body. BBB behavior scores of three groups are carried out in1d,1w,2w,4w,6w and8w respectively after UCBNSCs and PBS transplantation. Take7 SD rats from PBS injection group and UCBNSCs transplantation group each, getspinal cord injury tissue samples and do gene chip analysis to identify thedifferentially expressed genes.2.After admission, we assess all the obsolete spinalcord injury patients with American Spinal Injury Association （ASIA）and measurethe residual urine with urethral catheterization. We got the the reserved umbilical cordblood and differentiate into neural stem cells(NSCs) which were collected at aconcentration of109/L.The cells were injected into subarachnoid space. Three monthsafter the transplantation, we reassessed all the patients with ASIA and measured theresidual urine. Through the results, we evaluate the treatment effect.Result The hind limbs function of SD rats does not appear damaged obviously insham-operation group, the symptoms of paralysis, tail activity obstacle and urinationdysfunction appeared in PBS injection control group and UCBNSCs transplantationgroup. As time goes on, the function of hind limbs recovered,1d and1w aftertransplantation, BBB score shows no statistical difference in both groups, statisticalsignificance appears postoperative2w,4w,6w and8w between the two groups (P <0.05). Lots of UCBNSCs accumulate around the lesions of SCI on4w,and have theability to survive at least8weeks.UCBNSCs rarely differentiated into neurons andglial cells on2w.We identified24genes that showed a greater than2-fold change inspinal cord injury tissues, including20genes up regulated and4genes downregulated. After the UCBNSCs transplantation, all the patients showed a stable lifeindication. Three months later, patients’ ASIA scores increase and the residual urinedecrease, both the sensation plane and Motor plane descend, all the dates havestatistical significance.Conclusion1.UCBNSCs transplantations in the rat spinal cord injury show exactcurative effect, compared with PBS control group, UCBNSCs transplantation grouphave24genes expression quantity change after8w of UCBNSCs transplants, mayhave a certain relationship with spinal cord function recovery of SCI, which may bethe basis for preliminary study of related gene therapy.2.UCBNSCs transplantation is a treatment which can improve the limb function and life quality of patients withobsolete spinal cord injury.