Repairing effect of human umbilical cord mesenchymal stem cells transplantation at different time points after spinal cord injury in adult rats

English Keywords:Umbilical cord mesenchymal stem cells  Spinal cord injury  Cell transplantation  Rat

English Abstract:

  【Abstract】 Objective：To observe the therapeutic effect of the human umbilical cord mesenchymal stem cells（hUCMSCs） transplantion at different time points after spinal cord injury in Wistar rats，and to explore the optimal time point of hUCMSCs transplantation for repairing spinal cord injury.Method：Eighty female Wistar rats were randomly divided into control group（group A），hUCMSCs transplantation 3d after injury（group B），hUCMSCs transplantation 1w after injury（group C） and hUCMSCs transplantation 3w after injury（group D）.The SCI animal model were induced by Impactor Model-Ⅱ at T10.Behavioral testing was performed 24 hours after injury，1 day pre-transplantation and post-transplantation weekly for 2 months according to Basso-Beattie-Bresnahan（BBB） open-field locomotor Rating Scale.Spinal cord tissues were subjected to immunohistochemical staining to detect the vascular regeneration and survival，and differentiation and migration of hUCMSCs.Result：BBB scores were no significant difference among all four groups 24 hours after SCI（P>0.05）.Before transplantation and 1 week after transplantation，there was also no significant difference between group D and group A，but group D had significantly higher score than group A at each time points from 2 weeks after transplantation（P<0.05）.The score of group A reached to a plateau at 9 weeks after SCI，which showed no statistical significance（P>0.05） compared with that at the end of experiment.BBB scores of group B，C and D increased gradually after transplantation，with significance noted between the consecutive time points in any group（P<0.05），and the score of group C was significantly higher than that of group B and D 6 weeks after transplantation（P<0.05）.Immunohistochemistry results showed absence of Brdu positive cell，abnormality of vascular shape absence of newborn vascular in group A；proliferation of glial cells with the characteristics of hypertrphy，disorder and scar formation around lesion site was evidenced.No BDA marked corticospinal tract was seen across the lesion site.Brdu positive cells were noted in group B，C and D，with the number of cells in group C and D more than that of group B.However，no differentiation to glial cell was evidenced in 3 groups.Group B and D had less and more disordered glial cells around lesion site than group A；the glial cells aroud lession site in group C was ordered and normal，with more regenerated vascular crossing corticospinal tract than that of group B and D.Conclusion：hUCMSCs transplantation after SCI can survive at least 2 months，which can inhibit glial scars formation，improve microcirculation of lesion site，and finally promote axonal regeneration as well as improving functional recovery.One week after SCI was the optimal time point.