Affiliation:
1. Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
3. Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Saitama, Japan
4. RIKEN-Keio University Joint Research Laboratory, Brain Science Institute, RIKEN, Saitama, Japan
Abstract
Abstract
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.
Funder
Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO); a grant from the Uehara Memorial Foundation
Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science and Technology of Japan
Project for the Realization of Regenerative Medicine and support for the core institutes for iPSC research from MEXT
“Funding Program for World-leading Innovative R&D on Science and Technology” to H.O. from the Ministry of Health, Labor, and Welfare
General Insurance Association of Japan; Research Fellowships for Young Scientists from the Japan Society for the Promotion of Science
Keio Gijuku Academic Development Funds
Grant-in-aid for the Global COE program from MEXT to Keio University
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Developmental Biology,Molecular Medicine
Cited by
125 articles.
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