Cellular and Molecular Neurobiology

, Volume 28, Issue 4, pp 529–543

The Therapeutic Effects of Tyrosine Hydroxylase Gene Transfected Hematopoetic Stem Cells in a Rat Model of Parkinson’s Disease

  • Shizhong Zhang
  • Zhihao Zou
  • Xiaodan Jiang
  • Ruxiang Xu
  • Wangming Zhang
  • Yuan Zhou
  • Yiquan Ke
Original Paper

Abstract

Aims

To investigate the therapeutic effects of tyrosine hydroxylase (TH)-transfected neuronal stem cells derived from bone marrow stem cells (NdSCs-D-BMSCs) on Parkinson’s disease (PD) through different transplantation protocols, including microinjection into the cerebral ventricles (CV) and the striatum (ST).

Methods

After identification by enzyme digestion, the constructed plasmid pEGFP-C2-TH was transfected into 8-day-cultured NdSCs-D-BMSCs by electroporation resulting in the coexpression of green fluorescent protein (GFP) and TH. The TH-transfected cells were injected into either the right ST or CV of PD rats. The changes in locomotor activity of PD rats and the migration of transplanted cells in cerebral tissue were monitored and cerebral DA levels were assayed by high performance liquid chromatography (HPLC).

Results

Five days after plasmid pEGFP-C2-TH transfection into NdSCs-D-BMSCs GFP was expressed in 62.1% of the cells and the rate of co-expression with TH was 83.5%. Ten weeks following transplantation, the symptoms of PD rats in both groups were significantly improved and DA levels were restored to 46.6% and 33% of control. The transferred cells showed excellent survival rates in PD rat brains and distant migration was observed.

Conclusion

Both CV and ST transplantation of TH-transfected NDSCs-D-BMSCs has obvious therapeutic effects on PD rats. This study could provide evidence for future transplantation route selection, possibly leading to stem cell transplantation through lumbar puncture.

Keywords

Gene therapy Neuronal stem cells derived from bone marrow stem cells Parkinson’s disease Rats Transplantation route 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Shizhong Zhang
    • 1
  • Zhihao Zou
    • 1
  • Xiaodan Jiang
    • 1
  • Ruxiang Xu
    • 1
  • Wangming Zhang
    • 1
  • Yuan Zhou
    • 1
  • Yiquan Ke
    • 1
  1. 1.Neuromedical Institute, Zhujiang HospitalSouth Medical UniversityGuangzhou CityP.R. China

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