Direct Differentiation of Adult Ocular Progenitors into Striatal Dopaminergic Neurons

Parkinson's disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson's disease.

A reliable method to induce neural stem cells directed differentiating into neurons in vitro / 解剖学报

Objective To introduce a reliable method to induce neural stem cells directed differentiating into neurons in vitro. Methods The rat neural stem cells were cultured in selected serum-free medium. After cultured for 2, 3 passages,the neurospheres or single-cells isolated from neurospheres were cultured in conditioned medium to induce directed differentiating into neurons. Besides morphological observation of those cells under inverted microscope, NSE immunocytochemistry was carried out to detect the differentiating ratio of those cells from neural stem cells into neurons. Results It was shown that the conditioned medium could induce neural stem cells differentiating into neurons effectively in both neurospheres culture mode or single-cells culture mode. Furthermore, compared with the neurospheres culture mode, the single-cells culture mode showed more synchronous in the differentiation process and higher in the percentage of NSE-positive cells. Conclusion This method can induce neural stem cells directed differentiating into neurons effectively and stablely.