Midbrain Neural Stem Cells Show Unique Cell Survival, Neuronal Commitment and Neurotrophic Properties with Therapeutic Potential for Parkinson?s Disease

Parkinson’s disease (PD) is one severe debilitating neurological disease that results from massive and progressive degenerative loss of dopaminergic neurons in the substantial nigra, and new cell therapy appeal hopeful functional recovery of injured dopaminergic neuronal system and cure of PD. We are interested in therapeutic potential of neural stem cell in transplantation treatment against PD, the midbrain-derived neural stem cells (mNSCs) were studied by in vitro culture in focusing on their proliferative, differentiation and neurotrophic properties and in comparing with hippocampus-derived NSCs (hNSCs). The results revealed that: 1) The mNSCs showed lower BrdU incorporation ratio or lower proliferative rate than that of hippocampus-derived ones but had higher cell survival capacity in serum-free culture; 2) The mNSCs exhibited similar Tuj-1+ immature neuronal differentiation, but higher Nurr1+ and tyrosine hydroxylase (TH)+ cell fate commitment in comparison with that of hNSCs in at d1-d7 differentiation culture; 3) The mNSCs expressed several neurotrophic factors, i.e. brainderived neurotrophic factor(BDNF), glial-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF) and DJ-1, that actively function in dopaminergic neuronal maintenance or neuroprotection, with their slightly different or similar levels in comparison to that of hNSCs. Taken together, this study has provided new evidence that mNSCs show the unique cell proliferation, cell survival, dopaminergic neuronal differentiation and neurotrophic properties, suggesting that midbrain-derived NSCs may present an ideal cell source or reliable tissue candidate for therapeutic cell transplantation or neuroprotective treatment of PD in human beings.