抗体芯片在干细胞治疗阿尔茨海默病研究中的应用
杂志名称：
Advanced Science（2023 IF：15.1）
文献题目：
HGF mediates clinical-grade human umbilical cord-derived mesenchymal stemcells improved functional recovery in a senescence-accelerated mouse model of Alzheimer’s disease
第一作者：
贾雅丽
通讯作者：
裴雪涛；岳文
作者单位：
军事科学院军事医学研究院
华南干细胞与再生医学研究所
解放军联勤保障部队920医院
发表时间：
2020-07
文献全文下载地址：
https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201903809
本实验所用产品：
品名：Human Cytokine Array G2000
货号：AAH-CYT-G2000（人174因子半定量抗体芯片）
详情：https://www.raybiotech.com/human-cytokine-array-g2000-aah-cyt-g2000
因子列表：
芯片类型：
实验样本：
细胞培养上清
研究背景
阿尔茨海默病(AD)是一种以神经元丢失和认知功能下降为特征的进行性神经退行性疾病。AD患者的大脑会出现两个标志性病变：β-淀粉样蛋白斑块和神经纤维缠结。目前，AD治疗方法都仅针对症状，无法延缓疾病病程。在前期，该团队首次发现人脐带来源的间充质干细胞（hUC-MSCs）能一定程度改善老化大脑的认知能力（PMID：28796260）。
思路&结果
1、Huc-MSCs可改善SAMP8小鼠的认知功能
将hUC-MSCs移植到AD衰老加速模型SAMP8小鼠体内，行为学测试结果显示hUC-MSCs移植能显著改善小鼠的认知功能。
2、Huc-MSCs可调节AD相关关键蛋白表达及促进AD小鼠内源性神经再生
Huc-MSCs可显著降低AD相关关键蛋白（p-Tau、BACE1、Pgsk3β、β-APP和PS1）的表达，从而减轻神经元损伤。并且，Huc-MSCs能够激活内源性神经发生，从而有利于稳定海马神经网络。
3、Huc-MSCs修复冈田酸诱导的AD细胞损伤
在体外AD细胞模型中，hUC-MSCs能有效地恢复和挽救冈田酸对神经细胞的损伤。
4、Huc-MSCs分泌的HGF可发挥对冈田酸诱导的AD细胞损伤的保护作用
使用RayBiotech蛋白芯片检测了三种不同脐带来源的Huc-MSCs 培养上清中174个已知细胞因子的蛋白表达水平。聚类分析结果显示不同组别间出现显著差异的蛋白(图4A)。进一步筛选其中荧光信号值大于1000的因子，最终确定了18个表达信号最强的因子(图4B)。在详细研究和分析各因子的作用后，从18个表达信号最强的因子筛选出四个可能参与损伤修复的因子（IL-6、HGF/hepatocyte growth factor 、Ang和GRO）。补充实验发现仅HGF可恢复受损的原代神经元。
为了探讨Huc-MSCs分泌的HGF是否参与Huc-MSC介导的神经损伤的修复，在MSC处理组中加入抗HGF的中和抗体(HGFAb)。结果表明Huc-MSCs分泌的HGF在Huc-MSCs介导的神经损伤修复中发挥重要作用（图4C-I)。
讨论 & 结论
Discussion & Conclusion
在本项研究中，作者用RayBiotech半定量蛋白芯片检测不同组别174个蛋白的表达水平。发现HGF在不同组别间出现显著的差异，进一步验证实验表明hUC-MSCs分泌的肝细胞生长因子HGF在hUC-MSCs修复AD大脑损伤神经细胞及提高认知的过程中发挥重要的调控作用。
近期优惠活动
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