Clinical applications of human neural stem cells in
neurodegenerative diseases, especially neonatal
hypoxic-ischemic brain injury and spinal cord injury
Authors
박국인
Citation
JOURNAL OF THE KOREAN MEDICAL ASSOCIATION, Vol.54(5) : 468-481, 2011
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.