Neurochemical Research

, Volume 43, Issue 4, pp 930–937 | Cite as

Human Neural Stem Cells with GDNF Site-Specific Integration at AAVS1 by Using AAV Vectors Retained Their Stemness

  • Jinju Zhang
  • Xiaomei Liu
  • Yun Zhang
  • Zuo Luan
  • Yinxiang Yang
  • Zhaoyan Wang
  • Chun Zhang
Original Paper


The neural stem cells (NSCs) have the ability to self-renew, and to migrate to pathologically altered regions of the central nervous system. Glial cell derived neurotrophic factor (GDNF) could protect dopamine neurons and rescue motor neurons in vivo, which has been proposed as a promising candidate for the treatments of degenerative neurological diseases. In order to combine the advantages of neurotrophic factors and stem cells in clinical therapy, we established the modified hNSCs that has site-specific integration of GDNF gene by using recombinant adeno-associated virus (rAAV) vectors. The hNSCs were co-infected by rAAV2-EGFP-GDNF and rAAV2-SVAV2 which provide integrase to specifically integrate GDNF gene into AAVS1 site. The GDNF-hNSCs maintained their original stem cell characteristics and the ability to differentiate into neurons in vitro. In the animal model, the GDNF-hNSCs were specifically transplanted into CA1 area of hippocampi and could migrate to the dentate gyrus region and differentiate into neuronal cells while maintaining GDNF expression. hNSCs with GDNF gene site-specific integration at AAVS1 by using AAV vectors retained their stemness and effectively expressed GDNF, which indicates the potential of employing transplanted hNPCs for treatment of brain injuries and degenerative neurological diseases.


Human neural stem cells (hNSCs) Glial-derived neurotrophic factor (GDNF) Gene therapy Recombinant adeno-associated virus (rAAV) 



This work was supported by Grants from the National Natural Science Foundation of China (81371670), the Key Technology Support Program of Jiangsu Province (Grant No. BE2014638), and the Science and Technology Program of Suzhou (Grant No. ZXY201432).

Compliance with Ethical Standards

Conflict of interest

The authors state no financial/commercial conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cell and Gene Therapy CenterSuzhou Institute of Biomedical Engineering and Technology, Chinese Academy of SciencesSuzhouPeople’s Republic of China
  2. 2.CAS Key Lab of Bio-Medical DiagnosticsSuzhou Institute of Biomedical Engineering and Technology, Chinese Academy of SciencesSuzhouPeople’s Republic of China
  3. 3.University of Chinese Academy of SciencesBeijingPeople’s Republic of China
  4. 4.Navy General Hospital of PLA ChinaBeijingPeople’s Republic of China

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