Research Of Transplantation Of Human Oligodendrocyte Precursor Cells By The Intra-cisterna Magna Approach In The Preterm Rats With White Matter Injury

Objective: To explore the therapeutic effect of human oligodendrocyte precursor cells(hOPCs)transplantation via intra-cisterna magna in rats model of white matter injury(WMI).Methods: All Sprague-Dawley rats were randomly divided into sham-operation group,model control group and transplantation group(n=10 each).The model control group and transplantation group underwent ligation of the right common carotidartery and were exposed to hypoxia for 2 hours to establish a rat model of WMI at postday3,the sham-operation group were only treated with right common carotidartery isolated.hOPCs were obtained from an aborted human fetus aged 11 weeks post-conception with voluntary abortion.hOPCs were transplanted via the cisterna magna in a WMI rat model.Behavioral tests were performed to evaluate neurological function,and electron microscopy were performed to observe myelin sheath thickness and remyelination.To assess white matter injury,the expression of MBP(myelin basic protein)was investigated by immunohistochemistry.To explore migration and survival of transplanted hOPCs in focal zone,antibodies specific to human cytoplasm(STEM121)and human nuclear antigen(HNA)was investigated at rats 12 weeks after transplantation by immunofluorescence staining.Results: In Morris Water Maze navigation test,the model control group had a significantly longer escape latency than the sham-operation group at P90.However,hOPCs transplantation decreased escape latency in the transplantation group versus the model control group(P<0.05).hOPCs transplantation improve neurological outcome to a certain extent at P90.Electron microscope images showed remyelination of brain after hOPCs transplantation in WMI rats.The model control group showed increased g-ratio(total axon diameter/total fiber diameter)compared to that in the sham-operation group.However,compared with that in the model control group,hOPCs transplantation in WMI rats had decreased g-ratio(p<0.05).MBP stain showed comparable rates between rats treated with hOPCs and those left untreated,and were higher than those in model control group(P<0.05).Immunofluorescence staining of hOPCs showed that transplanted hOPCs migrated to focal zone and survival successfully.Conclusions: 1.Transplanted hOPCs through intra-cisterna magna routine migrated and survived in the rat brain.2.hOPCs transplantation by intra-cisterna magna approach alleviated behavioral impairments and promoted myelination in the WMI rat model.