Author: Shi, Mengâ€meng; Yang, Qingâ€yuan; Monsel, Antoine; Yan, Jiaâ€yang; Dai, Chengâ€xiang; Zhao, Jingâ€ya; Shi, Guoâ€chao; Zhou, Min; Zhu, Xueâ€mei; Li, Suâ€ke; Li, Ping; Wang, Jing; Li, Meng; Lei, Jiâ€gang; Xu, Dong; Zhu, Yingâ€gang; Qu, Jieâ€ming
Title: Preclinical efficacy and clinical safety of clinicalâ€grade nebulized allogenic adipose mesenchymal stromal cellsâ€derived extracellular vesicles Cord-id: p5ac83vs Document date: 2021_8_14
ID: p5ac83vs
Snippet: Mesenchymal stromal cellâ€derived extracellular vesicles (MSCâ€EVs) turn out to be a promising source of cellâ€free therapy. Here, we investigated the biodistribution and effect of nebulized human adiposeâ€derived MSCâ€EVs (haMSCâ€EVs) in the preclinical lung injury model and explored the safety of nebulized haMSCâ€EVs in healthy volunteers. DiRâ€labelled haMSCâ€EVs were used to explore the distribution of nebulized haMSCâ€EVs in the murine model. Pseudomonas aeruginosaâ€induced murin
Document: Mesenchymal stromal cellâ€derived extracellular vesicles (MSCâ€EVs) turn out to be a promising source of cellâ€free therapy. Here, we investigated the biodistribution and effect of nebulized human adiposeâ€derived MSCâ€EVs (haMSCâ€EVs) in the preclinical lung injury model and explored the safety of nebulized haMSCâ€EVs in healthy volunteers. DiRâ€labelled haMSCâ€EVs were used to explore the distribution of nebulized haMSCâ€EVs in the murine model. Pseudomonas aeruginosaâ€induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, ILâ€6, TNFâ€Î± and ILâ€10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSCâ€EVs through the nebulized route. Twentyâ€four healthy volunteers were involved and received the haMSCâ€EVs once, ranging from 2 × 10(8) particles to 16 × 10(8) particles (MEXVT study, NCT04313647). Nebulizing haMSCâ€EVs improved survival rate to 80% at 96 h in P. aeruginosaâ€induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSCâ€EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSCâ€EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSCâ€EVs in lung injury diseases.
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