Neural stem cells LewisX+CXCR4+modify disease progression in an amyotrophic lateral sclerosis model
Neural stem cells LewisX+CXCR4+modify disease progression in an amyotrophic lateral sclerosis model
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DOI：
10.1093/brain/awm043
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发表时间：
2007-05-01
期刊：
影响因子：
14.5
通讯作者：
Comi, Giacomo P.
中科院分区：
文献类型：
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作者：
Corti, Stefania;Locatelli, Federica;Comi, Giacomo P.
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种以运动神经元变性为特征的致死性神经系统疾病。我们测试了超氧化物歧化酶（SODI）-G93 A转基因小鼠，ALS模型，神经干细胞亚群双阳性刘易斯X和趋化因子受体CXCR 4（LeX+ CXCR 4+）的治疗是否可以改变疾病的进展。在体外，暴露于形态发生刺激后，LeX+ CXCR 4+细胞在分化后产生胆碱能运动神经元样细胞。将来自在所有组织或仅在运动神经元中表达绿色荧光蛋白的小鼠的LeX+ CXCR 4+细胞在体外引发一段时间后移植到SODI-G93 A小鼠的脊髓中。脊髓的检查揭示了供体来源的细胞的整合，这些细胞主要分化为神经元，在运动神经元样细胞中的比例较低。脊髓运动神经元的定量表明LeX+ CXCR 4+细胞具有显著的神经保护作用。与对照组相比，VEGF和IGFI依赖性通路在移植动物中均被显著调节，表明这些神经营养因子在MN protection.Our结果支持神经干细胞组分通过神经发生和生长因子释放在运动神经元疾病中的治疗潜力。
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of the motor neurons. We tested whether treatment of superoxide dismutase (SODI)-G93A transgenic mouse, a model of ALS, with a neural stem cell subpopulation double positive for Lewis X and the chemokine receptor CXCR4 (LeX+CXCR4+) can modify the disease's progression. In vitro, after exposure to morphogenetic stimuli, LeX+CXCR4+ cells generate cholinergic motor neuron-like cells upon differentiation. LeX+CXCR4+ cells deriving from mice expressing Green Fluorescent Protein in all tissues or only in motor neurons, after a period of priming in vitro, were grafted into spinal cord of SODI-G93A mice.Transplanted transgenic mice exhibited a delayed disease onset and progression, and survived significantly longer than non-treated animals by 23 days. Examination of the spinal cord revealed integration of donor-derived cells that differentiated mostly in neurons and in a lower proportion in motor neuron-like cells. Quantification of motor neurons of the spinal cord suggests a significant neuroprotection by LeX+CXCR4+ cells. Both VEGF- and IGFI-dependent pathways were significantly modulated in transplanted animals compared to controls, suggesting a role of these neurotrophins in MN protection.Our results support the therapeutic potential of neural stem cell fractions through both neurogenesis and growth factors release in motor neuron disorders.