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OBJECTIVE: To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant. METHODS: A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×10(5) OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days. RESULTS: Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P < 0.05). CONCLUSIONS: OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 μmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.

To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children.Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later.No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P0.05).These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.

To study the clinical efficacy of transplantation of human neural progenitor cells (hNPCs) in the treatment of severe cerebral palsy (CP) in children.Forty-five children with CP were voluntarily accepted transplantation of hNPCs. The cells obtained from the forebrain of 10 to 12-week-fetus were cultured and amplified into hNPCs. Then the hNPCs were injected into the cerebral ventricle of the patients with the supersonic guidance.Dyssomnia, irritability and muscular tension were improved in one patient 3 days after transplantation. The clinical improvements were observed in the majority of the patients 1 month after transplantation. The therapeutic effects slowed down 3 to 6 months after transplantation. One year after transplantation the gross and fine motor skills and the congnition ability in the transplantation group were considerably surpassed to those in the control group. No delayed severe complications were observed after transplantation. No tumorigenesis was noted 5 years after transplantation.The transplantation of hNPCs as a novel therapy is effective and safe for severe CP. Many investigations are needed to evaluate the effect of the therapy.

To study the effect of hyperbaric oxygenation (HBO) on the differentiation of the implanted human neural stem cells (hNSCs) into neurons in neonatal rats following hypoxic-ischemic brain damage (HIBD).HIBD model was prepared by ligation of the left common carotid artery, followed by 8% hypoxia exposure in 7-day-old Sprague-Dawley rat pups. Three days later, the rats received implantation of hNSCs into the left cerebral ventricles. Then the survived rats were randomly divided into two groups: transplantation alone and transplantation+HBO (n=8 each). HBO treatment was administered (1.8 ATA, 1 hr once daily for 10 days) in the transplantation+HBO group 1 hr after hNSCs transplantation. Brains were removed 10 days after transplantation. Frozen coronal sections were prepared for immunofluorescence analysis to detect the neural differentiation of the transplanted cells in the cerebral cortex and hippocampus.Differentiated neurons of implanted cells distributed mainly in the cortex and the hippocampus of the injured side. There was no difference in the number of neurons in the cortex between the two groups, while the number of neurons in the hippocampus significantly increased in the transplantation+HBO group compared with that in the transplantation alone group (231.4+15.1 vs 162.6+5.6; P0.05).HBO treatment may promote the differentiation of implanted hNSCs into neurons in the hippocampus of neonatal rats following HIBD.