Clinical neuroscienceTransplanted adult spinal cord–derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury
Section snippets
Preparation and characterization of neurospheres
Spinal cord–derived NSPCs were cultured in our laboratory from the ependymal region of adult male Wistar rats expressing eGFP (original animals were obtained from E. Kobayashi, Utsunomiya, Togichi, Japan). All eGFP positive cells were derived from homozygous transgenic Wistar rats. The rats carried the eGFP transgene prepared from complementary deoxyribonucleic acid fragment and PCXN2 expression vector containing cytomegalovirus enhancer, chicken beta-actin enhancer-promoter and rabbit
Cell survival at 12 weeks
After transplantation of NSPCs 9 days after injury, 1.2% of the transplanted cells survived at 12 weeks (2320 cells), and most of the surviving cells were located at the periphery of the lesion site next to healthier tissue. The center of the lesion was severely cavitated and contained macrophages and cellular debris with few surviving transplanted cells. The majority of the transplanted cells had migrated toward and into the site of injury, however some transplanted cells remained around the
Discussion
Various types of stem/progenitor cells have been transplanted into experimental models of spinal cord injury (SCI) with promising results but minimal functional benefit, and phase 1 trials of stem/progenitor cells have already been performed in humans with SCI (Tator, 2006). In the present studies, we focused on adult spinal cord–derived NSPCs because they have the ability to regenerate the cord in lower species. In addition, BMSCs were examined because of their easy accessibility, potential
Acknowledgments
Technical support provided by Rita van Bendegem and Linda Lee. Assistance with microscopy provided by Sheer Ramjohn and Dr. Patrick Shannon of the Department of Cellular and Molecular Pathology, University of Toronto. Funding provided by the Canadian Institutes for Health Research (CIHR), the International Foundation of Research in Paraplegia, and the Christopher Reeve Paralysis Foundation.
References (47)
- et al.
Minimal criteria for defining multipotent mesenchymal stromal cellsThe International Society for Cellular Therapy position statement
Cytotherapy
(2006) - et al.
Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI
Exp Neurol
(2004) - et al.
Green fluorescent protein-transgenic rat: a tool for organ transplantation research
Biochem Biophys Res Commun
(2001) - et al.
Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement
Cytotherapy
(2005) - et al.
Identification of a neural stem cell in the adult mammalian central nervous system
Cell
(1999) - et al.
Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord
Biomaterials
(2006) - et al.
Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination
J Neurosci Methods
(2002) - et al.
The stem-cell menagerie
Trends Neurosci
(2003) Cellular transplantation strategies for spinal cord injury and translational neurobiology
NeuroRx
(2004)- et al.
Stem cells in the adult mammalian central nervous system
Curr Opin Neurobiol
(1999)
Tissue-engineered spinal cord
Transplant Proc
Elimination of basal lamina and the collagen “scar” after spinal cord injury fails to augment corticospinal tract regeneration
Exp Neurol
Estimation of nuclear population from microtome sections
Anat Rec
A sensitive and reliable locomotor rating scale for open field testing in rats
J Neurotrauma
Urodele spinal cord regeneration and related processes
Dev Dyn
Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation
Neuroreport
Human long-term bone marrow culture
Reaction of spinal cord central canal cells to cord transection and their contribution to cord regeneration
J Comp Neurol
Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord
Eur J Neurosci
Neural stem cell lineages are regionally specified, but not committed, within distinct compartments of the developing brain
Development
Allodynia limits the usefulness of intraspinal neural stem cell grafts: directed differentiation improves outcome
Nat Neurosci
Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery
Proc Natl Acad Sci U S A
Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord
J Neurosci
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