Abstract
Several studies have reported functional improvement after transplantation of neural stem cells into injured spinal cord. We now provide evidence that grafting of adult neural stem cells into a rat thoracic spinal cord weight-drop injury improves motor recovery but also causes aberrant axonal sprouting associated with allodynia-like hypersensitivity of forepaws. Transduction of neural stem cells with neurogenin-2 before transplantation suppressed astrocytic differentiation of engrafted cells and prevented graft-induced sprouting and allodynia. Transduction with neurogenin-2 also improved the positive effects of engrafted stem cells, including increased amounts of myelin in the injured area, recovery of hindlimb locomotor function and hindlimb sensory responses, as determined by functional magnetic resonance imaging. These findings show that stem cell transplantation into injured spinal cord can cause severe side effects and call for caution in the consideration of clinical trials.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Behavior, Animal
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Brain / blood supply
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Brain / physiopathology
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Bromodeoxyuridine / metabolism
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Calcitonin Gene-Related Peptide / metabolism
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Cell Count
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Disease Models, Animal
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Female
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Functional Laterality / physiology
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Hindlimb / innervation
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Hindlimb / physiopathology
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Immunohistochemistry / methods
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Laminin / classification
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Laminin / metabolism
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Magnetic Resonance Imaging / methods
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Motor Activity / physiology
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Myelin Sheath / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Pathways / metabolism
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Neurofilament Proteins / metabolism
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Neurons / physiology*
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Oligopeptides / metabolism
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Oxygen / blood
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Pain / etiology
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Pain / physiopathology
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Pain Measurement
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Phosphopyruvate Hydratase / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Atrial Natriuretic Factor / metabolism
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Recovery of Function / physiology*
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Spinal Cord / metabolism
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Spinal Cord / physiopathology
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Spinal Cord Injuries / physiopathology
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Spinal Cord Injuries / therapy*
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Stem Cell Transplantation / adverse effects
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Stem Cell Transplantation / methods*
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Stem Cells / physiology*
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Time Factors
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Transduction, Genetic / methods
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Tubulin / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Laminin
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Nerve Tissue Proteins
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Neurofilament Proteins
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Neurog2 protein, mouse
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Oligopeptides
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RNAIII inhibiting peptide
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Tubulin
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Green Fluorescent Proteins
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Phosphopyruvate Hydratase
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Receptors, Atrial Natriuretic Factor
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atrial natriuretic factor receptor C
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Bromodeoxyuridine
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Calcitonin Gene-Related Peptide
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Oxygen