Exp Neurobiol.  2020 Apr;29(2):130-137. 10.5607/en20011.

Intracerebral Transplantation of BDNF-overexpressing Human Neural Stem Cells (HB1.F3.BDNF) Promotes Migration, Differentiation and Functional Recovery in a Rodent Model of Huntington’s Disease

  • 1Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea
  • 2CHA Stem Cell Institute, Department of Biomedical Science, CHA University, Seongnam 13488, Korea
  • 3Division of Magnetic Imaging Resonance, Korea Basic Science Institute, Cheongju 28119, Korea
  • 4Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Th e First Affi liated Hospital of Sun Yat-sen University, Guangzhou 510080, China
  • 5iPS Bio, Inc., Seongnam 13522, Korea


Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by abnormally expanded CAG repeats in the huntingtin gene. The huntingtin gene mutation leads to the progressive degeneration of striatal GABAergic medium spiny neurons (MSN) and reduces the level of brain-derived neurotrophic factor (BDNF) in HD patient’s brain. BDNF is an essential neurotrophic factor for the cortico-striatal synaptic activity and the survival of GABAergic neurons. In this study, we transplanted BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) into the contra-lateral side of unilateral quinolinic acid (QA)-lesioned striatum of HD rat model. The results of in vivo transplantation were monitored using various behavioral tests, 4.7 T animal magnetic resonance imaging (MRI) and immunohistochemical staining. We observed that the QA-lesioned rats receiving HB1.F3.BDNF cells exhibited significant behavioral improvements in the stepping, rotarod and apomorphine-induced rotation tests. Interestingly, contralaterally transplanted cells were migrated to the QA-lesioned striatum and the size of lateral ventricle was reduced. Histological analyses further revealed that the transplanted cells, which had migrated to the QA lesion site, were differentiated into the cells of GABAergic, MSN-type neurons expressing DARPP-32, and neural networks were established between the transplanted cells and the host brain, as revealed by retrograde tracing. Finally, there was a significant reduction of inflammatory response in HB1.F3.BDNF-transplanted HD animal model, compared with vehicle-transplanted group. Taken together, these results suggest that HB1.F3.BDNF can be an effective therapeutic strategy to treat HD patients in the future.


Huntington’s disease (HD); Neural stem cells; Brain-derived neurotrophic factor (BDNF); Magnetic resonance imaging (MRI); Behavioral recovery
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