Human Olfactory Bulb Neural Stem Cells Mitigate Movement Disorders in a Rat Model of Parkinson's disease.

Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells(NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DAneurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide atherapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the humanolfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, andprovide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactorybulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted intothe striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eightweeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (252.88%), neuronlike(52.634.16%), and astrocyte -like (22.361.56%) lineages, which we differentiated based on morphological andimmunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacologicalbehavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as apromising cell-based therapeutic strategy for Parkinson's disease.