Affiliations: Center for Gene Therapy, Tulane University, New
Orleans, LA, USA | Division of Clinical Neurophysiology, Karolinska
Institutet, Stockholm, Sweden | Department of Neuroscience, Karolinska Institutet,
Stockholm, Sweden
Note: [] Corresponding author: M. Birdsall Abrams, Department of
Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm,
Sweden. Tel.: +46 8 52487051; Fax: +46 8 323 742; E-mail:
[email protected]
Abstract: Purpose: Previous reports established that after a contusion injury
to the rat spinal cord, locomotor function was enhanced by the transplantation
of cells from bone marrow referred to as either mesenchymal stem cells or
multipotent mesenchymal stromal cells (MSCs). It has also been established that
neural stem cells (NSCs) enhance locomotor function after transplantation into
the injured rat spinal cord. However, the beneficial effects of NSCs are
limited by graft-induced allodynia-like responses. Little is known about the
effects of MSCs on sensory function in spinal cord injury. Therefore, the
objective of this research was to determine whether transplantation of MSCs
into the injured rat spinal cord induces allodynia-like responses. Methods: Contusion injuries of two different severities were induced
in rats to examine the effects of transplantation with MSCs on sensorimotor
deficits. The effects of MSCs on chronic inflammation were investigated, since
inflammation is reported to have a role in the sensorimotor deficits associated
with spinal cord injury. In addition, observations in other models suggest that
MSCs possess immunosuppressive effects. Results: We found that in contrast to previous observations with the
transplantation of neural stem cells, transplantation of MSCs did not induce
allodynia. MSCs attenuated injury-induced sensitivity to mechanical stimuli but
had no effect on injury-induced sensitivity to cold stimuli. MSCs also
significantly attenuated the chronic inflammatory response as assayed by GFAP
immunoreactivity for reactive astrocytes and ED1 immunoreactivity for activated
macrophages/microglia. In addition, transplantation of MSCs increased white
matter volumes and decreased cyst size in sections of the cord containing the
lesion. Conclusion: The results suggest that the sensorimotor enhancements
produced by MSCs can at least in part be explained by
anti-inflammatory/immunosuppressive effects of the cells, similar to such
effects of these cells observed in other experimental models.
