Glial cell derived neurotrophic factor (
GDNF) holds promises for treating
neurodegenerative diseases such as
Parkinson's disease. Human neural stem cells (hNSCs) have proved to be a suitable cell delivery vehicle for the safe and efficient introduction of
GDNF into the brain. In this study, we used hNSCs-infected with a lentivirus encoding
GDNF and the
hygromycin resistance gene as such vehicles. A modified
tetracycline operator 7 (tetO7) was inserted into a region upstream of the EF1-α promoter to drive
GDNF expression. After
hygromycin selection, hNSCs were infected with a lentivirus encoding a KRAB-
tetracycline repressor fusion
protein (TTS). TTS bound to tetO7 and suppressed the expression of
GDNF in hNSCs. Upon administration of
doxycycline (Dox) the TTS-tetO7 complex separated and the expression of
GDNF resumed. The hNSCs infected with
GDNF expressed the neural stem cell specific markers,
nestin and sox2, and exhibited no significant change in proliferation rate. However, the rate of apoptosis in hNSCs expressing
GDNF was lower compared with normal NSCs in response to
actinomycin treatment. Furthermore, a higher percentage of Tuj-1 positive cells were obtained from
GDNF-producing NSCs under conditions that induced differentiation compared to control NSCs. The inducible expression of
GDNF in hNSCs may provide a system for the controllable delivery of
GDNF in patients with
neurodegenerative diseases.