Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles - Sorbonne Université
Journal Articles Journal of Extracellular Vesicles Year : 2021

Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles

Abstract

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) turn out to be a promising source of cell-free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose-derived MSC-EVs (haMSC-EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC-EVs in healthy volunteers. DiR-labelled haMSC-EVs were used to explore the distribution of nebulized haMSC-EVs in the murine model. Pseudomonas aeruginosa-induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL-6, TNF-α and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC-EVs through the nebulized route. Twenty-four healthy volunteers were involved and received the haMSC-EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC-EVs improved survival rate to 80% at 96 h in P. aeruginosa-induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC-EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC-EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC-EVs in lung injury diseases.
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Dates and versions

hal-03562078 , version 1 (08-02-2022)

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Meng‐meng Shi, Qing‐Yuan Yang, Antoine Monsel, Jia‐Yang Yan, Cheng‐xiang Dai, et al.. Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles. Journal of Extracellular Vesicles, 2021, 10 (10), pp.12. ⟨10.1002/jev2.12134⟩. ⟨hal-03562078⟩
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