Elsevier

Neuroscience

Volume 155, Issue 3, 26 August 2008, Pages 760-770
Neuroscience

Clinical neuroscience
Transplanted adult spinal cord–derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury

https://doi.org/10.1016/j.neuroscience.2008.05.042Get rights and content

Abstract

We examined the effect of spinal cord–derived neural stem/progenitor cells (NSPCs) after delayed transplantation into the injured adult rat spinal cord with or without earlier transplantation of bone marrow–derived mesenchymal stromal cells (BMSCs). Either BMSCs or culture medium were transplanted immediately after clip compression injury (27 g force), and then, 9 days after injury, NSPCs or culture medium were transplanted. Cell survival and differentiation, functional recovery, retrograde axonal tracing, and immunoelectron microscopy were assessed. A significant improvement in functional recovery based on three different measures was seen only in the group receiving NSPCs without BMSCs, and the improved recovery was evident within 1 week of transplantation. In this group, NSPCs differentiated mainly into oligodendrocytes and astrocytes, there was ensheathing of axons at the injury site by transplanted NSPCs, an increase in host oligodendrocytes, and a trend toward an increase in retrogradely labeled supraspinal nuclei. Transplantation of the BMSC scaffold resulted in a trend toward improved survival of the NSPCs, but there was no increase in function. Thus, transplantation of adult rat NSPCs produced significant early functional improvement after spinal cord injury, suggesting an early neuroprotective action associated with oligodendrocyte survival and axonal ensheathment by transplanted NSPCs.

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.

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