Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis.
Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis.
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脂肪干细胞条件培养基延长肌萎缩侧索硬化症小鼠模型的存活时间
DOI：
10.1038/srep16953
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发表时间：
2015-11-20
影响因子：
4.6
通讯作者：
Du Y
中科院分区：
文献类型：
--
作者：
Fontanilla CV;Gu H;Liu Q;Zhu TZ;Zhou C;Johnstone BH;March KL;Pascuzzi RM;Farlow MR;Du Y
脂肪基质细胞（ASC）分泌各种营养因子，在各种神经元死亡模型中帮助保护神经元。在这项研究中，我们测试了人ASC条件培养基（ASC-CM）在表达突变型超氧化物歧化酶（SOD 1G 93 A）的人肌萎缩侧索硬化（ALS）转基因小鼠模型中的作用。用ASC-CM治疗有症状的SOD 1G 93 A小鼠显著增加了发病后存活时间和寿命。此外，在免疫组织化学分析中，给予ASC-CM治疗的SOD 1G 93 A小鼠在脊髓的早期症状阶段显示出高运动神经元计数、小胶质细胞和星形胶质细胞的较少活化。用ASC-CM处理7天的SOD 1G 93 A小鼠显示脊髓中磷酸化p38（pp 38）水平降低，这是一种参与炎症和神经元死亡的促分裂原活化蛋白激酶。此外，在用ASC-CM处理3天的SOD 1G 93 A小鼠中，脊髓中α-II血影蛋白的水平也受到抑制。有趣的是，神经生长因子（NGF），一种在ASC-CM中发现的神经营养因子，在SOD 1G 93 A小鼠神经退行性变的保护中发挥了重要作用。这些结果表明，ASC-CM有可能发展成为一种新的和有效的治疗ALS的治疗方法。
Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1G93A). Treating symptomatic SOD1G93A mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1G93A mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1G93A mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1G93A mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1G93A mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS.
影响因子：
2.5
作者：
Shimko MJ;Zaccone EJ;Thompson JA;Schwegler-Berry D;Kashon ML;Fedan JS
通讯作者：
Fedan JS