Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 2005 Mar;8(3):346-53
Date
02/16/2005Pubmed ID
15711542DOI
10.1038/nn1405Scopus ID
2-s2.0-20044370811 (requires institutional sign-in at Scopus site) 548 CitationsAbstract
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.
Author List
Hofstetter CP, Holmström NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, Wiesenfeld-Hallin Z, Kurpad SN, Frisén J, Olson LAuthor
Shekar N. Kurpad MD, PhD Chair, Director, Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Basic Helix-Loop-Helix Transcription Factors
Behavior, Animal
Brain
Bromodeoxyuridine
Calcitonin Gene-Related Peptide
Cell Count
Disease Models, Animal
Female
Functional Laterality
Green Fluorescent Proteins
Hindlimb
Immunohistochemistry
Laminin
Magnetic Resonance Imaging
Motor Activity
Myelin Sheath
Nerve Tissue Proteins
Neural Pathways
Neurofilament Proteins
Neurons
Oligopeptides
Oxygen
Pain
Pain Measurement
Phosphopyruvate Hydratase
Rats
Rats, Sprague-Dawley
Receptors, Atrial Natriuretic Factor
Recovery of Function
Spinal Cord
Spinal Cord Injuries
Stem Cell Transplantation
Stem Cells
Time Factors
Transduction, Genetic
Tubulin