期刊
STEM CELL REVIEWS AND REPORTS
卷 6, 期 2, 页码 186-198出版社
HUMANA PRESS INC
DOI: 10.1007/s12015-010-9152-3
关键词
Stem cell; Neural crest; Epidermal neural crest stem cell; EPI-NCSC; Spinal cord; Spinal cord injury; Somatosensory evoked potential; Semmes-Weinstein touch test
资金
- North East England Stem Cell Institute, Newcastle University
- Biomedical Technology Alliance of Southeastern Wisconsin
- Bryon Riesch Paralysis Foundation, Milwaukee
- Fraternal Order of Eagles Midwest Chapter
- National Spinal Cord Injury Association Milwaukee Chapter
- Falk Medical Research Trust
- MRC [G0802547] Funding Source: UKRI
- Medical Research Council [G0802547] Funding Source: researchfish
Here we show that epidermal neural crest stem cell (EPI-NCSC) transplants in the contused spinal cord caused a 24% improvement in sensory connectivity and a substantial recovery of touch perception. Furthermore we present a novel method for the ex vivo expansion of EPI-NCSC into millions of stem cells that takes advantage of the migratory ability of neural crest stem cells and is based on a new culture medium and the use of microcarriers. Functional improvement was shown by two independent methods, spinal somatosensory evoked potentials (SpSEP) and the Semmes-Weinstein touch test. Subsets of transplanted cells differentiated into myelinating oligodendrocytes. Unilateral injections of EPI-NCSC into the lesion of midline contused mouse spinal cords elicited bilateral improvements. Intraspinal EPI-NCSC did not migrate laterally in the spinal cord or invade the spinal roots and dorsal root ganglia, thus implicating diffusible factors. EPI-NCSC expressed neurotrophic factors, angiogenic factors, and metalloproteases. The strength of EPI-NCSC thus is that they can exert a combination of pertinent functions in the contused spinal cord, including cell replacement, neuroprotection, angiogenesis and modulation of scar formation. EPI-NCSC are uniquely qualified for cell-based therapy in spinal cord injury, as neural crest cells and neural tube stem cells share a higher order stem cell and are thus ontologically closely related.
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