间充质干细胞
细胞外小泡
细胞生物学
肺纤维化
小泡
纤维化
细胞外
干细胞
细胞
化学
生物
病理
医学
膜
生物化学
作者
Yaoying Long,Byoung-Chul Yang,Qian Lei,Fei Gao,Li Chen,Wenlan Chen,Si-Yi Chen,Wenxiang Ren,Yue Cao,Liuyue Xu,Di Wu,Jiao Qu,Li He,Yong A. Yu,Anyuan Zhang,Shan Wang,Weiqun Chen,Hongxiang Wang,Ting Chen,Zhichao Chen,Qiubai Li
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-02-21
标识
DOI:10.1021/acsnano.3c10547
摘要
Type 2 alveolar epithelial cell (AEC2) senescence is crucial to the pathogenesis of pulmonary fibrosis (PF). The nicotinamide adenine dinucleotide (NAD+)-consuming enzyme cluster of differentiation 38 (CD38) is a marker of senescent cells and is highly expressed in AEC2s of patients with PF, thus rendering it a potential treatment target. Umbilical cord mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have emerged as a cell-free treatment with clinical application prospects in antiaging and antifibrosis treatments. Herein, we constructed CD38 antigen receptor membrane-modified MSC-EVs (CD38-ARM-MSC-EVs) by transfecting MSCs with a lentivirus loaded with a CD38 antigen receptor-CD8 transmembrane fragment fusion plasmid to target AEC2s and alleviate PF. Compared with MSC-EVs, the CD38-ARM-MSC-EVs engineered in this study showed a higher expression of the CD38 antigen receptor and antifibrotic miRNAs and targeted senescent AEC2s cells highly expressing CD38 in vitro and in naturally aged mouse models after intraperitoneal administration. CD38-ARM-MSC-EVs effectively restored the NAD+ levels, reversed the epithelial-mesenchymal transition phenotype, and rejuvenated senescent A549 cells in vitro, thereby mitigating multiple age-associated phenotypes and alleviating PF in aged mice. Thus, this study provides a technology to engineer MSC-EVs and support our CD38-ARM-MSC-EVs to be developed as promising agents with high clinical potential against PF.
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