Transplantation of Neural Progenitor Cells Expressing Glial Cell Line-Derived Neurotrophic Factor into the Motor Cortex as a Strategy to Treat Amyotrophic Lateral Sclerosis
Transplantation of Neural Progenitor Cells Expressing Glial Cell Line-Derived Neurotrophic Factor into the Motor Cortex as a Strategy to Treat Amyotrophic Lateral Sclerosis
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DOI：
10.1002/stem.2825
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发表时间：
2018-07-01
期刊：
影响因子：
5.2
通讯作者：
Svendsen, Clive N.
中科院分区：
文献类型：
--
作者：
Thomsen, Gretchen M.;Avalos, Pablo;Svendsen, Clive N.
早期皮质运动神经元功能障碍可能是肌萎缩侧索硬化症(ALS)发病的基础。因此，皮质是肌萎缩侧索硬化症研究的关键领域，也是一个有希望的治疗靶点。在目前的研究中，将能够分泌胶质细胞源性神经营养因子(GDNF)的人皮质源性神经前体细胞移植到SOD1(G93A)ALS大鼠的皮质，在那里它们迁移、成熟为星形胶质细胞，并释放GDNF。这保护了运动神经元，延缓了疾病的病理，延长了动物的生存时间。这些被注射到食蟹猴大脑皮质的细胞存活了下来，并显示出强大的GDNF表达，没有不良反应。综上所述，这些数据表明，引入皮质星形胶质细胞释放GDNF代表了一种治疗ALS的新的有希望的方法。
Early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical area of ALS research and a promising therapeutic target. In the current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (GDNF) were transplanted into the SOD1(G93A) ALS rat cortex, where they migrated, matured into astrocytes, and released GDNF. This protected motor neurons, delayed disease pathology and extended survival of the animals. These same cells injected into the cortex of cynomolgus macaques survived and showed robust GDNF expression without adverse effects. Together this data suggests that introducing cortical astrocytes releasing GDNF represents a novel promising approach to treating ALS.