Transplantation of glial-committed progenitor cells into a viral model of multiple sclerosis induces remyelination in the absence of an attenuated inflammatory response.
Transplantation of remyelination-competent cells represents a promising strategy for the treatment of demyelinating diseases. As the environment dictates the success or failure of remyelination, it is critical to understand the role that the immune system plays in transplant-mediated remyelination. In this study, we evaluated the severity of neuroinflammation following transplantation of glial-committed progenitor cells into the spinal cords of mice chronically infected with mouse hepatitis virus (MHV), a model in which T cells and macrophages are critical in amplifying the severity of demyelination. Transplantation was performed following viral persistence in which inflammation and demyelination are established and clinical disease is evident. Mice were sacrificed 10 and 21 days following progenitor cell transplantation and the effect on neuroinflammation evaluated. Treatment did not alter accumulation of T cells or macrophages within the CNS as compared to control mice. Moreover, progenitor cell implantation did not affect local cytokine/chemokine gene expression in the CNS. Finally, remyelination associated with transplantation did not result in an imbalance of T(H)1-associated cytokine production by virus-specific T cells. These studies demonstrate that progenitor cell-mediated remyelination is not the result of modulating the composition of the cellular infiltrate nor cytokine expression by virus-specific T cells and suggest that remyelination may not depend on amelioration of the inflammatory response or alteration of cytokine secretion by virus-specific T cells.
Hardison
Jenny L
JL
Department of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine, 92697-3900, USA.
Nistor
Gabriel
G
Gonzalez
Rafael
R
Keirstead
Hans S
HS
Lane
Thomas E
TE
D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009103:Multiple Sclerosis / Q000209:etiology / Q000601:surgery* / Q000821:virology; D006517:Murine hepatitis virus / Q000472:pathogenicity; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009457:Neuroglia / Q000502:physiology*; D020556:Neutrophil Infiltration; D018121:Receptors, Cytokine / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D012260:Ribonucleases / Q000494:pharmacology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*
D016207:Cytokines; D018121:Receptors, Cytokine; D012260:Ribonucleases