Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
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Human Neural Stem Cells: Translational Research for Neonatal Hypoxic-Ischemic Brain Injury

  • Shin, Jeong Eun (Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Han, Jungho (Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Lim, Joo Hee (Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Eun, Ho Seon (Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine) ;
  • Park, Kook In (Division of Neonatology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine)
  • Received : 2018.08.03
  • Accepted : 2018.11.29
  • Published : 2019.02.28
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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.

Keywords

Acknowledgement

이 논문에 서술된 연구들은 한국연구재단과 보건의료기술 연구개발사업 지원을 받아 수행되었습니다(NRF; 2013M3A9B4076545, HI14C1564, HI16C1089). 기술적 도움을 주신 연세-칼자이스 이미징센터에 감사 드립니다.

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