Therapeutic potential of human olfactory bulb neural stem cells for spinal cord injury in rats.
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STUDY DESIGN: Adult human olfactory bulb neural stem cells (OBNSCs) were isolated from human patients undergoing craniotomy for tumor resection. They were genetically engineered to overexpresses green fluorescent protein (GFP) to help trace them following engraftment. Spinal cord injury (SCI) was induced in rats using standard laminectomy protocol, and GFP-OBNSC were engrafted into rat model of SCI at day 7 post injury. Three rat groups were used: (i) Control group, (ii) Sham group (injected with cerebrospinal fluid) and treated group (engrafted with OBNSCs). Tissues from different groups were collected weekly up to 2 months. The collected tissues were fixed in 4% paraformaldehyde, processed for paraffin sectioning, immunohistochemically stained for different neuronal and glial markers and examined with bright-field fluorescent microscopy. Restoration of sensory motor functions we assessed on a weekly bases using the BBB score. OBJECTIVES: To assess the therapeutic potential of OBNSCs-GFP and their ability to survive, proliferate, differentiate and to restore lost sensory motor functions following their engraftment in spinal cord injury (SCI). METHODS: GFP-OBNSC were engrafted into a rat model of SCI at day 7 post injury and were followed-up to 8 weeks using behavioral and histochemical methods. RESULTS: All transplanted animals exhibited successful engraftment. The survival rate was about 30% of initially transplanted cells. Twenty-seven percent of the engrafted cells differentiated along the NG2 and O4-positive oligodendrocyte lineage, 16% into MAP2 and β-tubulin-positive neurons, and 56% into GFAP-positive astrocytes. CONCLUSION: GFP-OBNSCs had survived for >8 weeks after engraftment and were differentiated into neurons, astrocytes and oligodendrocytes, The engrafted cells were distributed throughout gray and white matter of the cord with no evidence of abnormal morphology or any mass formation indicative of tumorigenesis. However, the engrafted cells failed to restore lost sensory and motor functions as evident from behavioral analysis using the BBB score test.