Mesenchymal Stem Cells-Derived Exosomes Alleviate Acute Lung Injury By Inhibiting Alveolar Macrophage Pyroptosis

被引：16

作者：

Liu, Peipei ^{[1
,2
]}

Yang, Shengnan ^{[1
,3
]}

Shao, Xuecheng ^{[4
]}

Li, Chen ^{[1
,5
]}

Wang, Zai ^{[6
]}

Dai, Huaping ^{[1
,2
,7
]}

Wang, Chen ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, China Japan Friendship Hosp, Inst Resp Med, Natl Ctr Resp Med,Natl Clin Res Ctr Resp Dis,Dept, Beijing, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Beijing, Peoples R China

[3] Harbin Med Univ, Harbin, Peoples R China

[4] Tianjin Third Cent Hosp, Dept Obstet Med, Tianjin, Peoples R China

[5] China Capital Med Univ, Beijing, Peoples R China

[6] China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China

[7] 2 Yinghua East Rd, Beijing 10029, Peoples R China

来源：

STEM CELLS TRANSLATIONAL MEDICINE | 2024年 / 13卷 / 04期

基金：

中国国家自然科学基金;

关键词：

mesenchymal stem cells; exosomes; acute lung injury; pyroptosis; caspase-1; RESPIRATORY-DISTRESS-SYNDROME; CASPASES; SOCIETY; DEATH;

D O I：

10.1093/stcltm/szad094

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Acute lung injury (ALI) is an important pathological process of acute respiratory distress syndrome, yet there are limited therapies for its treatment. Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to be effective in suppressing inflammation. However, the effects of MSCs-Exo on ALI and the underlying mechanisms have not been well elucidated. Our data showed that MSCs-Exo, but not exosomes derived from MRC-5 cells (MRC-5-Exo), which are human fetal lung fibroblast cells, significantly improved chest imaging, histological observations, alveolocapillary membrane permeability, and reduced inflammatory response in ALI mice model. According to miRNA sequencing and proteomic analysis of MSCs-Exo and MRC-5-Exo, MSCs-Exo may inhibit pyroptosis by miRNAs targeting caspase-1-mediated pathway, and by proteins with immunoregulation functions. Taken together, our study demonstrated that MSCs-Exo were effective in treating ALI by inhibiting the pyroptosis of alveolar macrophages and reducing inflammation response. Its mechanism may be through pyroptosis-targeting miRNAs and immunoregulating proteins delivered by MSCs-Exo. Therefore, MSCs-Exo may be a new treatment option in the early stage of ALI. Graphical Abstract

引用

页码：371 / 386

页数：16