Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 85, Issue 1, Pages 47-57Publisher
WILEY
DOI: 10.1002/jnr.21098
Keywords
cholinergic neurons; cell therapy; transplantation; differentiation
Categories
Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS011255, P01NS039161, R01NS046025] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS39161, R01 NS046025, NS11255] Funding Source: Medline
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Grafted human neural stem cells (hNSCs) may help to alleviate functional deficits resulting from spinal cord injury by bridging gaps, replacing lost neurons or oligodendrocytes, and providing neurotrophic factors. Previously, we showed that primed hNSCs differentiated into cholinergic neurons in an intact spinal cord. In this study, we tested the fate of hNSCs transplanted into a spinal cord T10 contusion injury model. When grafted into injured spinal cords of adult male rats on either the same day or 3 or 9 days after a moderate contusion injury, both primed and unprimed hNSCs survived for 3 months postengraftment only in animals that received grafts at 9 days postinjury. Histological analyses revealed that primed hNSCs tended to survive better and differentiated at higher rates into neurons and oligodendrocytes than did unprimed counterparts. Furthermore, only primed cells gave rise to cholinergic neurons. Animals receiving primed hNSC grafts on the ninth day postcontusion improved trunk stability, as determined by rearing activity measurements 3 months after grafting. This study indicates that human neural stem cell fate determination in vivo is influenced by the predifferentiation stage of stem cells prior to grafting. Furthermore, stem cell-mediated facilitation of functional improvement depends on the timing of transplantation after injury, the grafting sites, and the survival of newly differentiated neurons and oligodendrocytes. (c) 2006 Wiley-Liss, Inc.
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