Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein. Unfortunately, there has yet been any effective treatment so far for SCA1. This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells (HUMSCs) into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region. 106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age. HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice. HUMSCs transplantation effectively reduced the cerebellar atrophy, salvaged Purkinje cell death, and alleviated molecular layer shrinkage. Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation. At 5 months after transplantation, HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells. Our findings provide hope for a new therapeutic direction for the treatment of SCA1.

中文翻译：

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来自沃顿胶的人脐带间充质干细胞的异种移植可改善小鼠脊髓小脑共济失调 1 型

脊髓小脑性共济失调 1 型 (SCA1) 是一种常染色体显性神经退行性疾病，由 ATXN1 基因中 CAG 重复序列的扩增导致 ATXN1 蛋白中多聚谷氨酰胺重复序列的扩增引起。不幸的是，迄今为止对于SCA1还没有任何有效的治疗方法。本研究调查了将人脐带间充质干细胞 (HUMSC) 移植到转基因 SCA1 小鼠体内的可行性，该小鼠的 ATXN1 编码区含有 82 个重复的扩展不间断等位基因。106个人类脐带间充质干细胞在1个月大时被移植到小脑中。与未移植的SCA1小鼠相比，HUMSC在平衡木测试和旷场测试中对SCA1小鼠的运动行为表现出显着的改善作用。HUMSCs移植有效减少小脑萎缩，挽救浦肯野细胞死亡，并减轻分子层萎缩。电生理学研究表明，干细胞移植后神经元肌肉对刺激的反应强度增加，表明复合运动动作电位的振幅更高。移植后 5 个月，分散在小鼠小脑中的 HUMSC 仍然存活并分泌细胞因子，但未分化为神经元或神经胶质细胞。我们的研究结果为 SCA1 的治疗提供了新的治疗方向。