Evaluation of Mesenchymal Stem Cells and Granulocyte Colony Stimulating Factor in Treatment of Complete Spinal Cord Injury

2018 ◽  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cord Injury ◽  
Complete Spinal Cord Injury ◽  
Stimulating Factor

Efficacy of the coadministration of granulocyte colony-stimulating factor and stem cell factor in the activation of intrinsic cells after spinal cord injury in mice

2010 ◽  
Vol 13 (4) ◽  
pp. 516-523 ◽  
Author(s):  
Takahiro Osada ◽  
Masahiko Watanabe ◽  
Atsuhiro Hasuo ◽  
Masaaki Imai ◽  
Kaori Suyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Motor Function ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cord Injury ◽  
Stimulating Factor

Object Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that induces undifferentiated stem cells from the bone marrow (BM) into the peripheral blood. Stem cell factor (SCF) is also a hematopoietic cytokine that stimulates the differentiation and proliferation of neural stem cells and has neuroprotective effects. In cerebrally infarcted mice, the combination of G-CSF and SCF promotes the differentiation of BM-derived cells into neural cells, stimulates the proliferation of intrinsic neural stem cells, and improves motor function. The object of this study was to investigate the effects of these cytokines on BM stem cells, intrinsic cells, and motor function recovery in spinal cord–injured mice. Methods For marking BM-derived cells, the authors induced contusive spinal cord injury in mice transplanted with BM cells from green fluorescent protein (GFP)–transgenic mice after whole-body irradiation. These mice were treated with G-CSF and SCF in the subacute injury phase. Bromodeoxyuridine (BrdU) was injected into these mice to label proliferating cells. The cell numbers and phenotype of the BM-derived cells were evaluated, and the change in intrinsic cells (proliferation, accumulation, and differentiation) was noted using immunohistological analysis at 4 weeks postinjury (wpi). A behavior analysis was conducted until 12 wpi using the Basso, Beattie, Bresnahan locomotor rating scale. Results In the SCF + G-CSF group, improvement in hindlimb motor function was significantly greater than in the SCF group, G-CSF group, and sham-treatment (vehicle) group after 8 wpi. At 4 wpi, the number of GFP+ BM-derived cells induced in the lesion did not significantly differ between groups. At 4 wpi, the authors evaluated perilesional GFP− intrinsic spinal cord cells. The number of GFP− and F4/80+ cells was significantly greater in the SCF + G-CSF group than in the other 3 groups. As compared with the sham group, the number of NG2+/BrdU+ cells was significantly increased in the SCF + G-CSF group. Conclusions In this study, the combined administration of SCF and G-CSF in traumatic spinal cord injury not only improved motor function, but also induced the accumulation of intrinsic microglia and the active proliferation of intrinsic oligodendrocyte precursor cells.

scholarly journals Clinical Study of NeuroRegen Scaffold Combined with Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury

2017 ◽  
Vol 26 (5) ◽  
pp. 891-900 ◽  
Author(s):  
Yannan Zhao ◽  
Fengwu Tang ◽  
Zhifeng Xiao ◽  
Guang Han ◽  
Nuo Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Perioperative Complications ◽  
Motor Evoked Potential ◽  
Neurophysiological Monitoring ◽  
Human Umbilical Cord ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair.

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