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KMID : 1204720150080010106
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International Journal of Stem Cells
2015 Volume.8 No. 1 p.106 ~ p.114
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Direct Differentiation of Adult Ocular Progenitors into Striatal Dopaminergic Neurons
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Ahmad Iqbal
Zhao Xing
Parameswaran Sowmya
Destache Christopher J.
Rodriguez-Sierra Jorge
Thoreson Wallace B.
Ahmad Hiba
Sorrentino John
Balasubramanian Sudha
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Abstract
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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.
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KEYWORD
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Parkinson’s disease, Dopaminergic neurons, Directed differentiation, Stem cells
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