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KMID : 0614720110540050468
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Journal of Korean Medical Association
2011 Volume.54 No. 5 p.468 ~ p.481
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Clinical applications of human neural stem cells in neurodegenerative diseases, especially neonatal hypoxic-ischemic brain injury and spinal cord injury
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Park Kook-In
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Abstract
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Multipotent neural stem cells (NSCs) are operationally defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating CNS regions. The recognition that NSCs that were propagated in culture could be reimplanted into the mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that heretofore had been refractory to intervention. Proliferating single cells were isolated from the telencephalic region of human fetal cadavers at 13 weeks of gestation and were grown as neurospheres in long-term cultures. We investigated the characteristics of the growth, differentiation, and region-specific gene expression of human NSCs. An intriguing phenomenon with possible therapeutic potentials has begun to emerge from our observations of the behavior of NSCs in animal models of neonatal hypoxic-ischemic brain and spinal cord injury. During phases of active neurodegeneration, factors seem to be transiently elaborated to which NSCs may respond by migrating to degenerating regions and differentiating specifically towards replacement of dying neural cells. NSCs may attempt to repopulate and reconstitute ablated regions. In addition, NSCs may serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy. After the approval of the Institutional Review Board of Severance Hospital, Yonsei University College of Medicine and Korean Food and Drug Administration, an investigator-sponsored clinical trial of the transplantation of human NSCs into patients with severe perinatal hypoxic ischemic brain injury and traumatic cervical motor complete spinal cord injury have been performed. The existing data from these clinical trials have shown to be safe, well tolerated, and of neurologically-some benefits.
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KEYWORD
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Neural stem cells, Hypoxic-ischemic brain injury, Spinal cord injuries, Cell therapy
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