Journal
STEM CELLS
Volume 29, Issue 12, Pages 1983-1994Publisher
WILEY
DOI: 10.1002/stem.767
Keywords
Spinal cord injury; Neural stem cell; Stem-cell transplantation; Oligodendrocytes; Remyelination; shiverer mutant mouse
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Funding
- National Institute of Biomedical Innovation (NIBIO)
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (JSPS)
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Ministry of Health, Labor, and Welfare
- General Insurance Association of Japan
- Japan Society for the Promotion of Science
- Keio Gijuku Academic Development Funds
- Grants-in-Aid for Scientific Research [22791397] Funding Source: KAKEN
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Previous reports of functional recovery from spinal cord injury (SCI) in rodents and monkeys after the delayed transplantation of neural stem/progenitor cells (NS/PCs) have raised hopes that stem cell therapy could be used to treat SCI in humans. More research is needed, however, to understand the mechanism of functional recovery. Oligodendrocytes derived from grafted NS/PCs remyelinate spared axons in the injured spinal cord. Here, we studied the extent of this remyelination's contribution to functional recovery following contusive SCI in mice. To isolate the effect of remyelination from other possible regenerative benefits of the grafted cells, NS/PCs obtained from myelin-deficient shiverer mutant mice (shi-NS/PCs) were used in this work alongside wild-type NS/PCs (wt-NS/PCs). shi-NS/PCs behaved like wt-NS/PCs in vitro and in vivo, with the exception of their myelinating potential. shi-NS/PC-derived oligodendrocytes did not express myelin basic protein in vitro and formed much thinner myelin sheaths in vivo compared with wt-NS/PC-derived oligodendrocytes. The transplantation of shi-NS/PCs promoted some locomotor and electrophysiological functional recovery but significantly less than that afforded by wt-NS/PCs. These findings establish the biological importance of remyelination by graft-derived cells for functional recovery after the transplantation of NS/PCs into the injured spinal cord. STEM CELLS 2011;29:1983-1994
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