Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury.
OBJECTIVE
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.


CONCLUSIONS
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.
Abrams
M Birdsall
MB
Center for Gene Therapy, Tulane University, New Orleans, LA, USA. mathew.abrams@ki.se
Dominguez
Cecilia
C
Pernold
Karin
K
Reger
Roxanne
R
Wiesenfeld-Hallin
Zsuzsanna
Z
Olson
Lars
L
Prockop
Darwin
D
D000818:Animals; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006614:Hindlimb / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology* / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D039902:Multipotent Stem Cells / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D012684:Sensory Thresholds / Q000502:physiology; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors
D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein