Transplantation of adult neural stem cells modified to secrete GDNF has neuroprotective and restorative effect in ischemia model of rats

DOI 3 References
  • Kameda Masahiro
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Shingo Tetsuro
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Uozumi Takashi
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Matsui Toshihiro
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Miyoshi Yasuyuki
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Date Isao
    Department of Neurological Surgery, Okayama Univ. Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

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  • 虚血モデルに対する成体由来神経幹細胞を用いた神経再生・保護効果の検討

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Abstract

The aim of cell transplantation is to replace damaged area. But transplanted neural stem/progenitor cells (NSPCs) didn't treat lesion core. We transplanted adult NSPCs modified to secrete GDNF in order to make transplanted NSPCs replace ischemic area more effectively.<BR>NSPCs were harvested from subventricular zone (SVZ) of adult rats and cultured with EGF by using neurosphere technique. Expanded NSPCs were transfected with fiber-mutant F/RGD adenovirus containing GDNF (NSPC-GDNF) or EGFP (NSPC-EGFP) gene. The best transfection efficiency was derived from GDNF ELISA. At first, NSPC-GDNF or NSPC-EGFP cells were transplanted into the ischemic boundary zone of MCAO model of Wistar rats in the acute stage (allogenic transplantation). NSPC-GDNF group had a significantly better result in behavioral test and infarction volume than NSPC-EGFP group. Subsequently, NSPC-GDNF or NSPC-EGFP cells were transplanted into the damaged CAI of global ischemia model of Fischer344 rats in the chronic stage (syngenic transplantation). NSPC-GDNF cells migrated and differentiated into neuron as replacing the damaged CAI of hippocampus partially. Moreover, NSPC-GDNF group had shown the activation of neurogenesis of endogenous NSPCs.<BR>Consequently, we confirm NSPC-GDNF have neuroprotective effect and can replace damaged area. We think this result suggests that NSPC-GDNF cells can bring a good result in autologous-transplantation.

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