Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1α stabilization in the host brain

Kon Chu, Keun Hwa Jung, Se Jeong Kim, Soon Tae Lee, Juhyun Kim, Hee Kwon Park, Eun Cheol Song, Seung U. Kim, Manho Kim, Sang Kun Lee, Jae Kyu Roh

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia-inducible factor-1 (HIF-1) plays important roles in the prevention of cerebral ischemia. Deferoxamine (DFX), an iron chelator stabilizes the HIF-1α and activates target genes involved in compensation for ischemia. In this study, we are to investigate whether HIF-1α can be stabilized in human neural stem cells (NSCs) by DFX, and pre-transplantation of NSCs with HIF-1α stabilization can induce prolonged ischemic tolerance. In the DFX-treated NSCs, the HIF-1α protein expression was increased about 100-fold time-dependently, and subsequent transcriptional activation (VEGF, BDNF and CXCR4) was also observed. To test an ability to induce ischemic prevention in vivo, DFX-treated NSCs or naïve NSCs were transplanted in the striatum of adult rats. Seven days following the transplantation, focal cerebral ischemia was done. Infarct volumes were reduced in both NSCs-transplanted groups, compared with ischemia-only, but more reduced in DFX-treated NSCs group. The protective effects of NSCs were ablated when HIF-1α was silenced. HIF-1α protein levels were increased in both NSCs-transplanted groups, but more increased in DFX-treated NSCs group. RT-PCR analysis manifested a downregulation of mRNA expression of TNF-α, IL-6 and MMP-9 in both NSCs groups, but further decrease in DFX-treated NSCs group. These findings provide evidence that HIF-1α stabilization in human NSCs can be achieved effectively by DFX, and HIF-1α-stabilized NSCs protect against ischemia in a preventive mode.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
JournalBrain research
Volume1207
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Deferoxamine
  • Hypoxia-inducible factor-1
  • Ischemic prevention
  • Neural stem cell
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Transplantation of human neural stem cells protect against ischemia in a preventive mode via hypoxia-inducible factor-1α stabilization in the host brain'. Together they form a unique fingerprint.

Cite this