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Direct differentiation of adult ocular progenitors into striatal dopaminergic neurons.
International Journal of Stem Cells ( IF 2.3 ) Pub Date : 2015-5-29 , DOI: 10.15283/ijsc.2015.8.1.106
Iqbal Ahmad 1 , Xing Zhao 1 , Sowmya Parameswaran 1 , Christopher J Destache 2 , Jorge Rodriguez-Sierra 3 , Wallace B Thoreson 1 , Hiba Ahmad 1 , John Sorrentino 1 , Sudha Balasubramanian 1
Affiliation  

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.

中文翻译:

成人眼祖细胞直接分化为纹状体多巴胺能神经元。

帕金森氏病的特征是由于黑纹状体多巴胺能神经元的丧失而导致的运动功能障碍,是最常见的年龄相关性神经退行性疾病之一。鉴于目前尚无治愈方法,干细胞方法已成为替代因疾病逐渐丧失的多巴胺能神经元的可行治疗选择。该方法的成功可能取决于神经祖细胞的可及,可再生,免疫相容和非致瘤性来源,可以有效地产生稳定的多巴胺能神经元。在这里,我们证明了源自角膜缘的神经祖细胞是一种可再生的,可及的眼部组织,代表了多巴胺能神经元的安全来源。当角膜缘来源的神经祖细胞在Shh和FGF8的作用下经历成熟的定向分化方案时,它们获得了多巴胺能神经元的生化和功能表型,其中包括合成多巴胺的能力。他们在半帕金森病大鼠模型中进行纹状体内移植与苯丙胺诱导的旋转减少有关。移植后6周未观察到肿瘤形成。总之,这些发现将角膜缘来源的神经祖细胞假定为可用于帕金森氏病的潜在自体离体干细胞方法的多巴胺能神经元的可访问且安全的来源。他们在半帕金森病大鼠模型中进行纹状体内移植与苯丙胺诱导的旋转减少有关。移植后6周未观察到肿瘤形成。总之,这些发现将角膜缘来源的神经祖细胞假定为可用于帕金森氏病的潜在自体离体干细胞方法的多巴胺能神经元的可访问且安全的来源。他们在半帕金森病大鼠模型中进行纹状体内移植与苯丙胺诱导的旋转减少有关。移植后6周未观察到肿瘤形成。总之,这些发现将角膜缘来源的神经祖细胞假定为可用于帕金森氏病的潜在自体离体干细胞方法的多巴胺能神经元的可访问且安全的来源。
更新日期:2020-08-21
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