Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis
Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis
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DOI：
10.1006/exnr.2002.7860
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Sanberg, PR
中科院分区：
文献类型：
--
作者：
Garbuzova-Davis, S;Willing, AE;Sanberg, PR
移植来源于人畸胎瘤细胞系（NTera 2/D1）的hNT神经元已显示在许多损伤或疾病模型中改善运动功能障碍，其中缺陷相当局部化。然而，这些细胞以前没有在更广泛的神经变性模型中使用过。本研究的目的是确定hNT神经元移植对家族性肌萎缩侧索硬化症（FALS）小鼠模型中运动神经元功能的影响，其中在人SOD 1基因（G93 A）的位置93处存在丙氨酸取代甘氨酸。肌萎缩侧索硬化症是一种影响脊髓、脑干和皮质的致命性退行性运动神经元疾病。这种疾病在临床上表现为进行性肌无力和萎缩，导致瘫痪和诊断后3-5年内死亡。ALS占所有病例的10-13%。使用一系列行为测试来检查小鼠的自发运动活动、协调和肌肉力量。将hNT神经元长期（10-11周）移植到7周龄（在疾病的明显行为症状发作之前）的FALS（G93 A）小鼠的腹角脊髓的L-4-L-5节段中，将运动功能障碍的发作延迟至少3周。移植小鼠的平均寿命为128天，而培养基注射组的平均寿命为106天。hNT神经元移植组中的最后一只小鼠在135日龄时被安乐死，此时其显示后肢部分瘫痪。移植脊髓的免疫组织化学分析证实了移植的hNT神经元的存活，并且在植入部位附近显示出许多健康外观的运动神经元。这些结果表明，hNT神经元移植可能是ALS的一个有前途的治疗策略。(C)2002 Elsevier Science（美国）。
Transplantation of hNT Neurons derived from the human teratocarcinoma cell-line (NTera2/D1) has been shown to ameliorate motor dysfunction in a number of injury or disease models in which the deficits are fairly localized. However, these cells have not been used before in a model with more extensive neurodegeneration. The aim of this study is to determine the effects of hNT Neuron transplants on motor neuron function in a mouse model of familial amyotrophic lateral sclerosis (FALS) in which there is a substitution of Alanine for Glycine at position 93 of the human SOD1 gene (G93A). Amyotrophic lateral sclerosis is a fatal degenerative motor neuron disease affecting the spinal cord, brainstem, and cortex. This disease clinically manifests as progressive muscular weakness and atrophy, leading to paralysis and death within 3-5 years of diagnosis. The FALS represents 10-13% of all cases. A range of behavioral tests was used to examine spontaneous locomotor activity, coordination, and muscle strength of mice. Long-term (10-11 weeks) transplantation of hNT Neurons into the L-4-L-5 segments of the ventral horn spinal cord of FALS(G93A) mice at 7 weeks of age (before onset of overt behavioral symptoms of disease) delayed the onset of motor dysfunction for at least 3 weeks. The average lifespan of the transplanted mice was 128 days compared to 106 days for media-injected group. The last mouse in the hNT Neuron transplanted group was euthanized at 135 days of age when it display partial paralysis of the hindlimbs. lmmunohistochemical analysis of the implanted spinal cords demonstrated the survival of grafted hNT Neurons and showed many healthy-appearing motor neurons near the implant site. These results suggest that hNT Neuron transplantation may be a promising therapeutic strategy for ALS. (C) 2002 Elsevier Science (USA).