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Open Access Intraventricularly Injected Olig2-NSCs Attenuate Established Relapsing-Remitting EAE in Mice

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Abstract:

In multiple sclerosis (MS), a chronic inflammatory relapsing demyelinating disease, failure to control or repair damage leads to progressive neurological dysfunction and neurodegeneration. Implantation of neural stem cells (NSCs) has been shown to promote repair and functional recovery in the acute experimental autoimmune encephalomyelitis (EAE) animal model for MS; the major therapeutic mechanism of these NSCs appeared to be immune regulation. In the present study, we examined the efficacy of intraventricularly injected NSCs in chronic relapsing experimental autoimmune encephalomyelitis (CREAE), the animal disease model that is widely accepted to mimic most closely recurrent inflammatory demyelination lesions as observed in relapsing‐remitting MS. In addition, we assessed whether priming these NSCs to become oligodendrocyte precursor cells (OPCs) by transient overexpression of Olig2 would further promote functional recovery, for example, by contributing to actual remyelination. Upon injection at the onset of the acute phase or the relapse phase of CREAE, NSCs as well as Olig2-NSCs directly migrated toward active lesions in the spinal cord as visualized by in vivo bioluminescence and biofluorescence imaging, and once in the spinal cord, the majority of Olig2-NSCs, in contrast to NSCs, differentiated into OPCs. The survival of Olig2-NSCs was significantly higher than that of injected control NSCs, which remained undifferentiated. Nevertheless, both Olig2-NSCs and NSC significantly reduced the clinical signs of acute and relapsing disease and, in case of Olig2-NSCs, even completely abrogated relapsing disease when administered early after onset of acute disease. We provide the first evidence that NSCs and in particular NSC-derived OPCs (Olig2-NSCs) ameliorate established chronic relapsing EAE in mice. Our experimental data in established neurological disease in mice indicate that such therapy may be effective in relapsing-remitting MS preventing chronic progressive disease.

Keywords: Multiple sclerosis; Oligodendrocyte; Remyelination

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368911X637443

Publication date: September 1, 2012

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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