Abstract
BackgroundSulfur mustard (SM) is a notorious chemical warfare agent that can cause severe acute lung injury (ALI), in addition to other lesions. Currently, effective medical countermeasures for SM are lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs) possess self-renewal and multipotent differentiation capacity. BMSCs can also migrate to inflammation and injury sites and exert anti-inflammatory and tissue repair functions. Here, we report the curative effect of BMSCs on SM-induced ALI in a mouse model.MethodsMice BMSCs were injected into mice via the tail vein 24 h after SM exposure. The distribution of BMSCs in mice was detected by fluorescence imaging. The therapeutic potential of BMSCs was evaluated by the calculating survival rate. The effects of BMSCs on lung tissue injury and repair assessment were examined by staining with H&E and measuring the lung wet/dry weight ratio, BALF protein level, and respiratory function. The effects of BMSCs on the infiltration and phenotypic alteration of inflammatory cells were analyzed by immunohistochemistry and flow cytometry. The levels of chemokines and inflammatory cytokines were examined using the Luminex Performance Assay and ELISA. RNA interference, western blotting, and ELISA were applied to explore the role of the TLR4 signaling pathway in the anti-inflammatory effects of BMSCs. The extent of tissue repair was analyzed by ELISA, western blotting, and immunohistochemistry.ResultsFluorescence imaging indicated that the lung is the major target organ of BMSCs after injection. The injection of BMSCs significantly improved the survival rate (p < 0.05), respiratory function, and related lung damage indexes (wet/dry weight ratio, total proteins in BALF, etc.) in mice. BMSC administration also reduced the level of pro-inflammatory cytokines, chemokines, and inflammatory cell infiltration, as well as affected the balances of M1/M2 and Th17/Treg. Furthermore, solid evidence regarding the effects of BMSCs on the increased secretion of various growth factors, the differentiation of alveolar epithelial cells, and the enhancement of cell barrier functions was also observed.ConclusionBMSCs displayed protective effects against SM-induced ALI by alleviating inflammation and promoting tissue repair. The present study provides a strong experimental basis in a mouse model and suggests possible application for future cell therapy.
Highlights
Sulfur mustard (2,2-dichlorodiethyl sulfide, SM), a highly toxic chemical warfare agent, was first used in World War I in 1917, causing the injury or death of thousands of victims [1]
Bone marrowderived mesenchymal stromal cells (BMSCs) were identified based on typical morphological observations with an inverted microscope, phenotypic determination with flow cytometry and multipotent differentiation capacity
The BMSC markers were determined by flow cytometry analyses (Fig. 2b)
Summary
Sulfur mustard (2,2-dichlorodiethyl sulfide, SM), a highly toxic chemical warfare agent, was first used in World War I in 1917, causing the injury or death of thousands of victims [1]. Exposure to SM can cause damage to the respiratory tract, eyes, skin, and multiple organ systems. Among these organs, pulmonary toxicity appears to be the major cause of mortality and morbidity. As the toxic mechanism has not been fully elucidated, there is currently no effective therapeutic treatment for SM exposure. Sulfur mustard (SM) is a notorious chemical warfare agent that can cause severe acute lung injury (ALI), in addition to other lesions. We report the curative effect of BMSCs on SM-induced ALI in a mouse model
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