Neonatal Med.  2019 Feb;26(1):1-16. 10.5385/nm.2019.26.1.1.

Human Neural Stem Cells: Translational Research for Neonatal Hypoxic-Ischemic Brain Injury

Affiliations
  • 1Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea. kipark@yuhs.ac
  • 2BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Neonatal hypoxic-ischemic (HI) brain injury is a major cause of neonatal mortality and long-term neurodevelopmental disabilities. Although promising neuroprotective interventions have been studied, the current management of HI brain injury has been limited to supportive measures and induced hypothermia. In addition to engrafting, migrating toward the damage sites and differentiating into multiple lineages, multipotent neural stem/progenitor cells (NSPCs) also provide trophic/immunomodulatory factors and integrate into the host neurons upon implantation into an HI-injured brain. However, NSPC-based therapies have shown poor cell survival and integration, poor differentiation or restricted differentiation into the glial lineages. Furthermore, to achieve full functional recovery following brain injury, the optimization of cell therapy is needed to recapitulate the precise migration of stem cells to the region of interest and the neural rewiring present in the brain microenvironment. Therefore, the efficacy of NSPCs in the treatment of CNS injury is currently insufficient. Human NSPCs (hNSPCs) were isolated from the forebrain of an aborted fetus at 13 weeks of gestation with full parental consent and the approval of the Institutional Review Board of the Yonsei University College of Medicine. Here, to enhance the regenerative ability of hNSPCs in HI brain injury, cells were either pretreated with pharmacological agents or engineered to serve as vehicles for gene delivery. Furthermore, when combined with a poly (glycolic acid)-based synthetic scaffold, hNSPCs provide a more versatile treatment for neonatal HI brain injury. Finally, hNSPCs transfected with zinc-doped ferrite magnetic nanoparticles for controlling both cell migration and differentiation offer a simple and smart tool for cell-based therapies.

Keyword

Neural stem cells; Hypoxia-ischemia, brain; Cell therapy; Genetic therapy

MeSH Terms

Aborted Fetus
Brain Injuries*
Brain*
Cell Movement
Cell Survival
Cell- and Tissue-Based Therapy
Ethics Committees, Research
Genetic Therapy
Humans*
Hypothermia, Induced
Hypoxia-Ischemia, Brain
Infant
Infant Mortality
Nanoparticles
Neural Stem Cells*
Neurons
Parental Consent
Pregnancy
Prosencephalon
Stem Cells
Translational Medical Research*
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