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Preconditioning mesenchymal stromal cells with flagellin enhances the anti?inflammatory ability of their secretome against lipopolysaccharide?induced acute lung injury.

ABSTRACT: Acute lung injury (ALI) is a complex condition frequently encountered in the clinical setting. The aim of the present study was to investigate the effect of conditioned media (CM) from human adipose?derived mesenchymal stromal cells (MSCs) activated by flagellin (F?CM), a Toll?like receptor 5 ligand, on inflammation?induced lung injury. In the in vitro study, RAW264.7 macrophages treated with F?CM had a higher proportion of cells with the M2 phenotype, lower expression of pro?inflammatory factors and stronger expression of anti?inflammatory genes compared with the CM from normal adipose?derived MSCs. Furthermore, in vivo experiments were performed in mice with ALI induced by intraperitoneal injection of lipopolysaccharide. F?CM significantly alleviated the lung exudation, inhibited inflammatory cell recruitment in lung tissues and decreased the concentration of inflammatory factors in the bronchoalveolar lavage fluid. These findings indicated that F?CM has superior anti?inflammation ability compared with CM, and that it may represent a promising therapeutic approach to the treatment of inflammation?induced ALI.

SUBMITTER: Li R

PROVIDER: S-EPMC7453612 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Preconditioning mesenchymal stromal cells with flagellin enhances the anti‑inflammatory ability of their secretome against lipopolysaccharide‑induced acute lung injury.

Li Rui R Li Yu Y Dong Xiaoyan X

Molecular medicine reports 20200728 4

Acute lung injury (ALI) is a complex condition frequently encountered in the clinical setting. The aim of the present study was to investigate the effect of conditioned media (CM) from human adipose‑derived mesenchymal stromal cells (MSCs) activated by flagellin (F‑CM), a Toll‑like receptor 5 ligand, on inflammation‑induced lung injury. In the in vitro study, RAW264.7 macrophages treated with F‑CM had a higher proportion of cells with the M2 phenotype, lower expression of pro‑inflammatory factor ...[more]

PMID: 32945411

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Project description:BackgroundIschemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown.MethodsIn this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics.ResultsOur findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.ConclusionOur in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.

Dataset Information

Preconditioning mesenchymal stromal cells with flagellin enhances the anti?inflammatory ability of their secretome against lipopolysaccharide?induced acute lung injury.

Publications

Preconditioning mesenchymal stromal cells with flagellin enhances the anti‑inflammatory ability of their secretome against lipopolysaccharide‑induced acute lung injury.

Similar Datasets

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