Exogenous Schwann Cells Migrate, Remyelinate and Promote Clinical Recovery in Experimental Auto-Immune Encephalomyelitis
Open Access
- 11 September 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (9), e42667
- https://doi.org/10.1371/journal.pone.0042667
Abstract
Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease.Keywords
This publication has 49 references indexed in Scilit:
- Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- Induced pluripotent stem cells for neural tissue engineeringBiomaterials, 2011
- CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelinationProceedings of the National Academy of Sciences of the United States of America, 2010
- Boundary Cap Cells are Highly Competitive for CNS Remyelination: Fast Migration and Efficient Differentiation in PNS and CNS Myelin-Forming CellsThe International Journal of Cell Cloning, 2009
- Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous systemBrain, 2009
- Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signalingNature Biotechnology, 2009
- Imaging Correlates of Leukocyte Accumulation and CXCR4/CXCL12 in Multiple SclerosisArchives of Neurology, 2009
- CXCL12 (SDF-1α) suppresses ongoing experimental autoimmune encephalomyelitis by selecting antigen-specific regulatory T cellsThe Journal of Experimental Medicine, 2008
- Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysisJournal of Neuroinflammation, 2008
- Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosisNature, 2003