Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease.
Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease.
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DOI：
10.1038/nn.2210
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发表时间：
2008-11
影响因子：
25
通讯作者：
Maragakis, Nicholas J.
中科院分区：
文献类型：
--
作者：
Lepore, Angelo C.;Rauck, Britta;Dejea, Christine;Pardo, Andrea C.;Rao, Mahendra S.;Rothstein, Jeffrey D.;Maragakis, Nicholas J.
肌萎缩侧索硬化症（ALS）的细胞异常不仅限于运动神经元。星形胶质细胞功能障碍发生在人ALS和SOD1G93A动物模型中。因此，使用谱系限制性星形胶质细胞前体、胶质细胞限制性前体（GRP）的移植来研究正常星形胶质细胞的局灶性富集的价值。将GRP移植到颈脊髓呼吸运动神经元池周围，呼吸运动神经元池是导致这种神经退行性疾病死亡的主要细胞。GRP在病变组织中存活，有效地分化为星形胶质细胞，并减少SOD1G93A大鼠颈髓中的小胶质细胞增生。GRP延长了生存期和疾病持续时间，减少了运动神经元的损失，并减缓了前肢运动和呼吸生理功能的下降。神经保护作用部分由主要的星形胶质细胞谷氨酸转运蛋白GLT 1介导。这些发现证明了基于移植的星形胶质细胞替代的可行性和有效性，并表明靶向多节段细胞递送至颈脊髓是减缓与ALS相关的局灶性运动神经元丢失的有前景的治疗策略。
Cellular abnormalities in amyotrophic lateral sclerosis (ALS) are not limited to motor neurons. Astrocyte dysfunction occurs in human ALS and SOD1G93A animal models. Therefore, the value of focal enrichment of normal astrocytes was investigated using transplantation of lineage-restricted astrocyte precursors, Glial-Restricted Precursors (GRPs). GRPs were transplanted around cervical spinal cord respiratory motor neuron pools, the principal cells responsible for death in this neurodegenerative disease. GRPs survived in diseased tissue, differentiated efficiently into astrocytes, and reduced microgliosis in SOD1G93A rat cervical spinal cord. GRPs extended survival and disease duration, attenuated motor neuron loss, and slowed declines in fore-limb motor and respiratory physiological function. Neuroprotection was mediated in part by the primary astrocyte glutamate transporter, GLT1. These findings demonstrate the feasibility and efficacy of transplantation-based astrocyte replacement, and show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy for slowing focal motor neuron loss associated with ALS.
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影响因子：
14.5
作者：
Corti, Stefania;Locatelli, Federica;Comi, Giacomo P.
通讯作者：
Comi, Giacomo P.
影响因子：
6.1
作者：
Lladó, J;Haenggeli, C;Maragakis, NJ
通讯作者：
Maragakis, NJ
影响因子：
5.3
作者：
Garbuzova-Davis, S;Willing, AE;Sanberg, PR
通讯作者：
Sanberg, PR
DOI：
10.1073/pnas.0401103101
发表时间：
2004-05-04
影响因子：
11.1
作者：
Harper, JM;Krishnan, C;Kerr, DA
通讯作者：
Kerr, DA
影响因子：
3.5
作者：
Lladó, J;Haenggeli, C;Rothstein, JD
通讯作者：
Rothstein, JD