Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury.

Human umbilical cord mesenchymal stem cells (UCMSCs) have recently been shown to hold great therapeutic potential for the treatment of spinal cord injury (SCI). However, the number of engrafted cells has been shown to decrease dramatically post-transplantation. Physioxia is known to enhance the paracrine properties and immune modulation of stem cells, a notion that has been applied in many clinical settings. We therefore hypothesized that preconditioning of UCMSCs in physioxic environment would enhance the regenerative properties of these cells in the treatment of rat SCI. UCMSCs were pretreated with either atmospheric normoxia (21% O2, N-UCMSC) or physioxia (5% O2, P-UCMSC). The MSCs were characterized using flow cytometry, immunocytochemistry, and real-time polymerase chain reaction. Furthermore, 10(5) N-UCMSC or P-UCMSC were injected into the injured spinal cord immediately after SCI, and locomotor function as well as cellular, molecular and pathological changes were compared between the groups. We found that N-UCMSC and P-UCMSC displayed similar surface protein expression. P-UCMSC grew faster, while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs. Compared to N-UCMSC, treatment with P-UCMSC was associated with marked changes in the SCI environment, with a significant increase in axonal preservation and a decrease in the number of caspase-3+ cells and ED-1+ macrophages. These changes were accompanied by improved functional recovery. Thus, the present study indicated that preculturing UCMSCs under 5% lowered oxygen physioxic conditions prior to transplantation improves their therapeutic potential for the treatment of SCI in rats.

A combination of taxol infusion and human umbilical cord mesenchymal stem cells transplantation for the treatment of rat spinal cord injury.

BACKGROUND AND PURPOSE: Studies have shown that the administration of Taxol, an anti-cancer drug, inhibited scar formation, promoted axonal elongation and improved locomotor recovery in rats after spinal cord injury (SCI). We hypothesized that combining Taxol with another promising therapy, transplantation of human umbilical mesenchymal stem cells (hUCMSCs), might further improve the degree of locomotor recovery. The present study examined whether Taxol combined with transplantation of hUCMSCs would produce synergistic effects on recovery and which mechanisms were involved in the effect. METHODS: A total of 32 rats subjected to SCI procedures were assigned to one of the following four treatment groups: phosphate-buffered saline (PBS, control), hUCMSCs, Taxol, or Taxol+hUCMSCs. Immediately after injury, hUCMSCs were transplanted into the injury site and Taxol was administered intrathecally for 4 weeks. Locomotor recovery was evaluated using the Basso, Beattie and Bresnahan locomotor (BBB) rating scale. Survival of the transplanted human cells and the host glial reaction in the injured spinal cord were studied by immunohistochemistry. RESULTS: Treatment with Taxol, hUCMSCs or Taxol+hUCMSCs reduced the extent of astrocytic activation, increased axonal preservation and decreased the number of caspase-3(+) and ED-1(+) cells, but these effects were more pronounced in the Taxol+hUCMSCs group. Behavioral analyses showed that rats in the Taxol+hUCMSCs group showed better motor performance than rats treated with hUCMSCs or Taxol only. CONCLUSIONS: The combination of Taxol and hUCMSCs produced beneficial effects in rats with regard to functional recovery following SCI through the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects.

Posterior fixation and fusion for treatment of Os odontoideum complicated by atlantoaxial dislocation / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the techniques and evaluate the therapeutic effect of posterior fixation and fusion in the treatment of Os odontoideum complicated by atlantoaxial dislocation.</p><p><b>METHODS</b>From March, 2007 to October, 2010, 10 patients with Os odontoideum (including 6 male and 4 female patients aged from 20 to 65 years, mean 39.8 years) were treated in our hospital. Before and after the operation, the patients underwent X ray, CT and MRI examinations to measure and evaluate the degree of dislocation and neural compression. After preoperative traction for 1-2 weeks, all the 10 patients showed deductible atlantoaxial dislocation. Through a posterior approach, Atlantoaxial pedicle screws fixation were performed in 9 cases, and C2/3 pedicle-Occiput screw fixation was performed in 1 case. All the patients wore cervical collars as external support for 3 months after the operation.</p><p><b>RESULTS</b>The mean operative time was 3 h in these patients with a mean intraoperative blood loss of 420 ml. The symptoms were relieved after the surgery in all the patients, who showed no neck pain or neurological defects. The patients were followed up for 6 to 52 months (mean 22 months), and bony fusion was observed in all the 10 cases within 6 to 8 months without such complications as internal fixation failure or redislocation of the atlas.</p><p><b>CONCLUSION</b>Patients with Os odontoideum complicated by atlantoaxial dislocation should undergo surgical stabilization to avoid severe neurological injury. Pedicle screw instrument in the atlas allows restoration of the spinal stability, short-segment fusion, and maximal preservation of the mobility of the neck.</p>

Combination of NEP 1-40 infusion and bone marrow-derived neurospheres transplantation inhibit glial scar formation and promote functional recovery after rat spinal cord injury.

BACKGROUND AND AIMS: Studies have shown that administration of NEP1-40, a Nogo-66 receptor antagonist peptide, improves locomotor recovery in rats. We hypothesize that combining NEP1-40 with another promising therapy, neural stem cell transplantation, might further improve the degree of locomotor recovery. In the present study, we examined whether NEP1-40 combined with bone marrow stromal cells-derived neurospheres (BMSC-NSs) transplantation would produce synergistic effects on recovery. MATERIAL AND METHODS: Adult Sprague-Dawley rats were subjected to spinal cord injury (SCI) at the T10 vertebral level. Immediately after injury, rats were administrated NEP1-40 intrathecally for 4 weeks. BrdU-labeled BMSC-NSs (2×105 ) were transplanted into the injured site 7 days after SCI. Locomotor recovery was assessed for 10 weeks with BBB scoring. Animals were perfused transcardially 10 weeks after contusion, and histological examinations were performed. RESULTS: The combined therapy group showed statistically better locomotor recovery than the control group at 7 weeks of contusion. Neither of the two single-agent treatments improved locomotor function. The average area of the cystic cavity was significantly smaller in the combined therapy group than in the control group. Fluorescence microscopic analysis showed that NEP1-40 dramatically inhibited the formation of glial scar and promoted the axons penetration into the scar barrier. CONCLUSION: This study revealed that BMSC-NSs and NEP 1-40 exhibit synergistic effects on recovery in rat SCI. This may represent a potential new strategy for the treatment of SCI.

Effects of rehabilitation training combined with bone marrow mesenchymai stem cell-derived neural stem cells transplantation on the expression of Nogo-A and NgR proteins after spinal cord injury / 中华物理医学与康复杂志

Objective To study the effects of rehabilitation training combined with the transplantation of bone marrow mesenchymal stem cells-derived neural stem cells (BMSC-D-NSCs) on the expression of Nogo-A and NgR protein in rats after spinal cord injury (SCI).Methods The spinal cords of eighty Sprague-Dawley rats were injured using a modified Allen′s impactor (H = 25 mm) at T10. The injured rats were randomly divided into a combination therapy group which was given rehabilitation training and cell transplants, a cell graft group, a rehabilitation training group and a control group. At the 7th day post SCI, BMSC-D-NSCs were transplanted into the injured spinal cords of the rats in the combination therapy and cell graft groups. Hindlimb movement was assessed using the BassoBeattie-Bresnahan (BBB) scale every week, and protein was extracted from the injured spinal cord tissue for Nogo-A and NgR determination by Western blotting at the 1st, 3rd and 7th day after cell transplantation.Results The average BBB score of the rats in the combination therapy group was significantly higher than that of the other groups from 2 weeks post transplantation. The scores in the rehabilitation training group were significantly higher than in the control group from the 5th week post transplantation. Western blotting showed high expression of Nogo-A and NgR protein 24 h post surgery, but these declined with time. For Nogo-A there was a significant difference among the groups at all three time points. In the combination therapy group the expression declined to a minimum by the 7th day. For NgR protein there was no significant difference between the 1st and 3rd day in any group.Conclusions Rehabilitation training combined with BMSC-D-NSC transplantation can have a synergistic effect on functional recovery from SCI. It can down regulate the expression of Nogo-A and NgR protein.