Exosomes Isolated From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Neuroinflammation and Reduce Amyloid-Beta Deposition by Modulating Microglial Activation in Alzheimer's Disease

被引：278

作者：

Ding, Mao ^{[1
]}

Shen, Yang ^{[1
]}

Wang, Ping ^{[2
]}

Xie, Zhaohong ^{[2
]}

Xu, Shunliang ^{[2
]}

Zhu, ZhengYu ^{[2
]}

Wang, Yun ^{[2
]}

Lyu, Yongtao ^{[3
]}

Wang, Dewei ^{[2
]}

Xu, Linlin ^{[2
]}

Bi, JianZhong ^{[2
]}

Yang, Hui ^{[2
]}

机构：

[1] Shandong Univ, Sch Med, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Hosp 2, Dept Med Neurol, Jinan 250033, Shandong, Peoples R China

[3] Shandong Prov Third Hosp, Dept Med Neurol, Jinan 250031, Shandong, Peoples R China

来源：

NEUROCHEMICAL RESEARCH | 2018年 / 43卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; Exosomes; Human umbilical cord mesenchymal stem cells; Neuroinflammation; Microglial activation; Amyloid-; peptides; INSULIN-DEGRADING ENZYME; BLOOD-BRAIN-BARRIER; APPSWE/PS1DE9 MOUSE MODEL; BONE-MARROW; MEMORY DEFICITS; STROMAL CELLS; EXPRESSION; MICE; INFLAMMATION; POLARIZATION;

D O I：

10.1007/s11064-018-2641-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid- peptide (A) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models. We observed that hucMSC-exosomes injection could repair cognitive disfunctions and help to clear A deposition in these mice. Moreover, we found that hucMSC-exosomes injection could modulate the activation of microglia in brains of the mice to alleviated neuroinflammation. The levels of pro-inflammatory cytokines in peripheral blood and brains of mice were increased and the levels of anti-inflammatory cytokines were decreased. We also treated BV2 cells with hucMSC-exosomes in culture medium. HucMSC-exosomes also had inflammatory regulating effects to alternatively activate microglia and modulate the levels of inflammatory cytokines in vitro.

引用

页码：2165 / 2177

页数：13

共 64 条

[1]

Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species [J].