羊膜间充质干细胞外泌体通过microRNA-21调控小胶质细胞极化治疗缺血性脑卒中的机制研究
批准号:
81960252
项目类别:
地区科学基金项目
资助金额:
33.7 万元
负责人:
武晓云
依托单位:
学科分类:
神经功能保护与功能调控
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
武晓云
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中文摘要
间充质干细胞(MSCs)为治疗缺血性脑卒中开创了新途径,课题组前期证实小胶质细胞在MSCs治疗缺血性脑卒中发挥重要作用,但机制尚不清楚。课题组前期通过特定培养条件获得羊膜间充质干细胞(AMMSCs)具有较强的免疫调节能力,并发现microRNA-21是AMMSCs外泌体中表达丰富,且有效调节巨噬细胞极化的microRNA。故此,本课题拟验证AMMSCs外泌体提高缺血性脑卒中抗炎和神经保护作用,并进一步验证AMMSCs外泌体通过转运microRNA-21至小胶质细胞,应用Western Blot和qRT-PCR技术,检测microRNA-21可能作用的靶基因PTEN和PDCD4及其下游信号通路关键蛋白NF-κB和AP-1的表达变化,阐明AMMSCs外泌体通过microRNA-21调控小胶质细胞极化发挥对缺血性脑损伤的神经保护机制,为临床应用MSCs及其外泌体治疗缺血性脑卒中提供理论依据。
英文摘要
Mesenchymal stem cells (MSCs) have opened up a new way for the treatment of ischemic stroke. Previous studies have confirmed that microglia plays an important role in the neuroprotection of MSCs for ischemic stroke, but the specific mechanism is still unclear. In our previous study, we obtained amniotic mesenchymal stem cells (AMMSCs) under specific serum-free culture conditions and found that microRNA-21 is the most abundant and effective microRNA in regulating macrophage polarization of AMMSCs exosomes. This project will validate the anti-inflammatory and neuroprotective effects of AMMSCs exosomes in rats with ischemic stroke. It was further verified that AMMSCs transported microRNA-21 to microglia cells through exosome. Western Blot and qRT-PCR were used to detect the expression changes of PTEN, PDCD4, which may be the target genes of microRNA-21 and their downstream signaling pathway key proteins, NF-kappa B and AP-1. It was also demonstrated that AMMSCs exosomes play a neuroprotective role in ischemic brain injury through microRNA-21 regulating microglial polarization. Nursing mechanism provides theoretical basis for clinical application of MSCs exosomes in the treatment of ischemic stroke.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Serum-Free Medium Enhances the Therapeutic Effects of Umbilical Cord Mesenchymal Stromal Cells on a Murine Model for Acute Colitis
无血清培养基增强脐带间充质基质细胞对急性结肠炎小鼠模型的治疗效果。
DOI:10.3389/fbioe.2020.00586
发表时间:2020-06-26
期刊:FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
影响因子:5.7
作者:Wu, Xiaoyun;Wu, Daocheng;Ma, Zhijie
通讯作者:Ma, Zhijie
DOI:10.1016/j.jcyt.2020.03.431
发表时间:2020-07-01
期刊:CYTOTHERAPY
影响因子:4.5
作者:Wu, Xiaoyun;Ma, Zhijie;Wu, Daocheng
通讯作者:Wu, Daocheng
Adipose-Derived Stem Cells From Patients With Ulcerative Colitis Exhibit Impaired Immunosuppressive Function.
来自溃疡性结肠炎患者的脂肪干细胞表现出免疫抑制功能受损
DOI:10.3389/fcell.2022.822772
发表时间:2022
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Wu X;Mu Y;Yao J;Lin F;Wu D;Ma Z
通讯作者:Ma Z
Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile.
脐带间充质基质细胞在无血清定义培养基中显示出改进的安全性。
DOI:10.1186/s13287-023-03604-0
发表时间:2023-12-12
期刊:Stem cell research & therapy
影响因子:7.5
作者:
通讯作者:
DOI:10.3389/fimmu.2023.1213161
发表时间:2023
期刊:Frontiers in immunology
影响因子:7.3
作者:
通讯作者:
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