Human glial progenitor engraftment and gene expression is independent of the ALS environment.
Human glial progenitor engraftment and gene expression is independent of the ALS environment.
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DOI：
10.1016/j.expneurol.2014.12.011
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发表时间：
2015-02
影响因子：
5.3
通讯作者：
Maragakis NJ
中科院分区：
文献类型：
--
作者：
Haidet-Phillips AM;Doreswamy A;Gross SK;Tang X;Campanelli JT;Maragakis NJ
虽然肌萎缩性侧索硬化症（ALS）是一种运动神经元疾病，但基础研究强调星形胶质细胞参与了疾病的进程。因此，用健康的星形胶质细胞替代患病的星形胶质细胞群的策略可以防止运动神经元变性。我们的研究试图用神经胶质限制性祖细胞（GRPs）来评估星形胶质细胞的替代，这是一种谱系限制性前体细胞，能够在移植后分化为星形胶质细胞。我们当前研究的目的是评估移植到患病的ALS脊髓与健康的野生型脊髓如何影响人类GRP植入和选择的基因表达。将人grp移植到ALS小鼠模型或野生型交配小鼠的脊髓中。小鼠在病程开始或疾病末期被处死进行分析。经免疫组化和NanoString®基因谱分析，移植后的GRPs在细胞的移植和基因表达方面均无明显差异。我们的数据表明，人类神经胶质祖细胞的植入和基因表达与神经退行性ALS脊髓环境无关。考虑到人类grp目前正处于ALS患者脊髓移植的临床开发阶段，这些发现很有意义。
Although Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, basic research studies have highlighted that astrocytes contribute to the disease process. Therefore, strategies which replace the diseased astrocyte population with healthy astrocytes may protect against motor neuron degeneration. Our studies have sought to evaluate astrocyte replacement using glial-restricted progenitors (GRPs), which are lineage-restricted precursors capable of differentiating into astrocytes after transplantation. The goal of our current study was to evaluate how transplantation to the diseased ALS spinal cord versus a healthy, wild-type spinal cord may affect human GRP engraftment and selected gene expression. Human GRPs were transplanted into the spinal cord of either an ALS mouse model or wild-type littermate mice. Mice were sacrificed for analysis at either the onset of disease course or at the endstage of disease. The transplanted GRPs were analyzed by immunohistochemistry and NanoString® gene profiling which showed no gross differences in the engraftment or gene expression of the cells. Our data indicate that human glial progenitor engraftment and gene expression is independent of the neurodegenerative ALS spinal cord environment. These findings are of interest given that human GRPs are currently in clinical development for spinal cord transplantation into ALS patients.