[PS11-2C-1] Human neural stem cells: Translational research for neonatal hypoxic-ischemic brain injury
Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Neural stem cells (NSCs) are characterized by a capacity for self-renewal, differentiation into neurons and glia, migration toward HI-injured sites, and improvement of the compromised environment in HI brain injury. NSCs expanded in culture could be implanted into the brain where they integrate into host neural circuitry and stably express foreign genes. It hence appears that transplantation of NSCs has been proposed as a promising therapeutic strategy in neonatal HI brain injury. During HI brain injury, factors seem to be elaborated to which NSCs respond by migrating to injured area and differentiating into neural cell types lost to HI injury. In addition, NSCs serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy (e.g. with factors that might enhance neuronal differentiation, neurites outgrowth, neuronal connection, neuroprotection, and/or immunomodulatory substances). When combined with certain synthetic biomaterials, NSCs may be even more effective in engineering the HI-damaged brain towards reconstitution. Human NSCs were isolated from the forebrain of an aborted fetus at 13 weeks of gestation with full parental consent and the approval of the IRB of Yonsei University College of Medicine (Permit No. 4-2003-0078). In this study, we investigate the therapeutic effects of proneuronal transcriptional factor, neurogenin-2- and anti-inflammatory factor IL-10-transduced human NSCs following transplantation into neonatal HI brain injury.