Source Paper
Soheila Karimi-Abdolrezaee, Eftekhar Eftekharpour, Jian Wang, Cindi M. Morshead, Michael G. Fehlings
Journal of Neuroscience • 2006
Spinal cord injury (SCI) results in loss of oligodendrocytes demyelination of surviving axons and severe functional impairment. Spontaneous remyelination is limited. Thus, cell replacement therapy is an attractive approach for myelin repair. In this study, we transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI. A combination of growth factors, the anti-inflammatory drug minocycline, and cyclosporine A immunosuppression was used to enhance the survival of transplanted adult NPCs. Our results show the presence of a substantial number of surviving NPCs in the injured spinal cord up to 10 weeks after transplantation at the subacute stage of SCI. In contrast, cell survival was poor after transplantation into chronic lesions. After subacute transplantation, grafted cells migrated >5 mm rostrally and caudally. The surviving NPCs integrated principally along white-matter tracts and displayed close contact with the host axons and glial cells. Approximately 50% of grafted cells formed either oligodendroglial precursor cells or mature oligodendrocytes. NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed the axons. We also observed that injured rats receiving NPC transplants had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses. Our data provide strong evidence in support of the feasibility of adult NPCs for cell-based remyelination after SCI.
Objective: Assessment of functional neurological recovery in injured rats receiving neural precursor cell (NPC) transplants using the Basso, Beattie, and Bresnahan Locomotor Rating Scale
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isolated from yellow fluorescent protein-expressing transgenic mice • not applicable • not mentioned • not mentioned
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Adult rats received spinal cord injury
Note: Injury was performed prior to NPC transplantation
“transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats”
Neural precursor cells were transplanted into the injured spinal cord at 2 weeks after injury, representing the subacute phase of spinal cord injury
Note: Subacute transplantation resulted in substantial NPC survival
“transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI”
Neural precursor cells were transplanted into the injured spinal cord at 8 weeks after injury, representing the chronic phase of spinal cord injury
Note: Chronic phase transplantation resulted in poor cell survival
“transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI”
Growth factors, minocycline, and cyclosporine A were administered to enhance survival of transplanted NPCs
Note: Combined treatment approach to improve NPC survival
“A combination of growth factors, the anti-inflammatory drug minocycline, and cyclosporine A immunosuppression was used to enhance the survival of transplanted adult NPCs”
Functional neurological recovery was assessed using the standardized Basso, Beattie, and Bresnahan Locomotor Rating Scale
Note: Assessment performed to measure locomotor function recovery
“injured rats receiving NPC transplants had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale”
Locomotor function was assessed using grid-walk analysis to evaluate footfall accuracy and motor coordination
Note: Complementary behavioral assessment method
“improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses”
Locomotor function was assessed through footprint analysis to evaluate gait patterns and motor recovery
Note: Complementary behavioral assessment method
“improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses”
Surviving NPCs were evaluated in the injured spinal cord up to 10 weeks after transplantation at the subacute stage
Note: Substantial number of surviving NPCs observed after subacute transplantation; poor survival after chronic transplantation
“Our results show the presence of a substantial number of surviving NPCs in the injured spinal cord up to 10 weeks after transplantation at the subacute stage of SCI. In contrast, cell survival was poor after transplantation into chronic lesions”
Migration of grafted cells was evaluated in the injured spinal cord
Note: Cells migrated greater than 5 mm rostrally and caudally after subacute transplantation
“After subacute transplantation, grafted cells migrated >5 mm rostrally and caudally”
Surviving NPCs were evaluated for integration along white-matter tracts and differentiation into oligodendroglial cells
Note: Approximately 50% of grafted cells formed oligodendroglial precursor cells or mature oligodendrocytes
“The surviving NPCs integrated principally along white-matter tracts and displayed close contact with the host axons and glial cells. Approximately 50% of grafted cells formed either oligodendroglial precursor cells or mature oligodendrocytes”
NPC-derived oligodendrocytes were evaluated for myelin basic protein expression and axon ensheathing
Note: NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed axons
“NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed the axons”
Rats received spinal cord injury and NPC transplants at 2 and 8 weeks after injury
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