Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice
Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice
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DOI：
10.1093/brain/awp318
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发表时间：
2010-02-01
期刊：
影响因子：
14.5
通讯作者：
Comi, Giacomo P.
中科院分区：
文献类型：
--
作者：
Corti, Stefania;Nizzardo, Monica;Comi, Giacomo P.
脊髓性肌萎缩症是一种无法治愈的遗传性神经系统疾病，可导致婴儿死亡。我们以前的研究表明，来源于脊髓的原代神经干细胞可以改善小鼠脊髓性肌萎缩症的表型，但这种原代来源的转化价值有限。在这里，我们说明了来自胚胎干细胞的多能干细胞显示出与来自脊髓的多能干细胞相同的潜在治疗效果，并作为用于移植的神经干细胞的无限来源提供了巨大的希望。我们发现胚胎干细胞来源的神经干细胞在体外和体内都可以分化为运动神经元。此外，鞘内移植到脊髓性肌萎缩症小鼠后，神经干细胞，如来自脊髓的神经干细胞，存活并迁移到适当的区域，改善行为终点和寿命，并表现出神经保护能力。使用药物选择性胚胎干细胞系获得的神经干细胞产生了最大的改善。与来自原代组织的细胞一样，胚胎干细胞衍生的神经干细胞适当地整合到实质中，表达神经元和运动神经元特异性标记。我们的研究结果表明，在神经干细胞介导的治疗中使用多能细胞的翻译潜力，并强调了神经上皮细胞药物选择的潜在安全性改善和益处。
Spinal muscular atrophy, characterized by selective loss of lower motor neurons, is an incurable genetic neurological disease leading to infant mortality. We previously showed that primary neural stem cells derived from spinal cord can ameliorate the spinal muscular atrophy phenotype in mice, but this primary source has limited translational value. Here, we illustrate that pluripotent stem cells from embryonic stem cells show the same potential therapeutic effects as those derived from spinal cord and offer great promise as an unlimited source of neural stem cells for transplantation. We found that embryonic stem cell-derived neural stem cells can differentiate into motor neurons in vitro and in vivo. In addition, following their intrathecal transplantation into spinal muscular atrophy mice, the neural stem cells, like those derived from spinal cord, survived and migrated to appropriate areas, ameliorated behavioural endpoints and lifespan, and exhibited neuroprotective capability. Neural stem cells obtained using a drug-selectable embryonic stem cell line yielded the greatest improvements. As with cells originating from primary tissue, the embryonic stem cell-derived neural stem cells integrated appropriately into the parenchyma, expressing neuron- and motor neuron-specific markers. Our results suggest translational potential for the use of pluripotent cells in neural stem cell-mediated therapies and highlight potential safety improvements and benefits of drug selection for neuroepithelial cells.