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Neurogenin-2-transduced human neural progenitor cells attenuate neonatal hypoxic-ischemic brain injury.

 Il-Shin Lee  ;  Kyo Yeon Koo  ;  Kwangsoo Jung  ;  Miri Kim  ;  Il-Sun Kim  ;  Kyujin Hwang  ;  Seokhwan Yun  ;  Haejin Lee  ;  Jeong Eun Shin  ;  Kook In Park 
 Translational Research, Vol.183 : 121-136, 2017 
Journal Title
 Translational Research 
Issue Date
Animals ; Animals, Newborn ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Brain Injuries/therapy* ; Cell Differentiation ; Cell Line, Tumor ; Cell Transplantation ; Gene Expression Regulation ; Humans ; Hypoxia-Ischemia, Brain/therapy* ; Mice ; Multipotent Stem Cells ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism* ; Neural Stem Cells/metabolism* ; Neurons/physiology ; Tissue Culture Techniques
Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury. NEUROG2- or green fluorescent protein (GFP)-encoding adenoviral vector-transduced hNPCs (NEUROG2- or GFP-NPCs) were transplanted into neonatal mouse brains with HI injury. Grafted NEUROG2-NPCs showed robust dispersion and engraftment, prolonged survival, and neuronal differentiation in HI brain injury. NEUROG2-NPCs significantly improved neurological behaviors, decreased cellular apoptosis, and increased the neurite outgrowth and axonal sprouting in HI brain injury. In contrast, GFP-NPC grafts moderately enhanced axonal extension with limited behavioral recovery. Notably, NEUROG2-NPCs showed increased secretion of multiple factors, such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NTF3), fibroblast growth factor 9 (FGF9), ciliary neurotrophic factor (CNTF), and thrombospondins 1 and 2 (THBS 1/2), which promoted SH-SY5Y neuroblastoma cell survival and neurite outgrowth. Thus, we postulate that NEUROG2-expressing human NPCs facilitate functional recovery after neonatal HI brain injury via their ability to secrete multiple factors that enhance neuronal survival and neuroplasticity.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실)
Yonsei Authors
박국인(Park, Kook In) ; 신정은(Shin, Jeong Eun)
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