The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard

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.Electronic supplementary materialThe online version of this article (10.1186/s13287-019-1189-x) contains supplementary material, which is available to authorized users.

Anti-inflammatory protein TSG-6 secreted by bone marrow mesenchymal stem cells attenuates neuropathic pain by inhibiting the TLR2/MyD88/NF-κB signaling pathway in spinal microglia

“…Consistent with our results, previous studies demonstrated that intrathecal delivery of BMSCs can relieve neuropathic pain and that the analgesic effect of BMSCs persists for at least 14 days [34,35]. Mesenchymal stem-cell therapy, such as BMSCs treatment, has been considered a potentially successful approach for treating various diseases including neuropathic pain [37,46], spinal cord injury [47,48], Alzheimer's disease [49,50], stroke [51,52], and lung injury [53,54]. BMSCs were the earliest and the most widely studied MSCs in vitro and in vivo.…”

Mesenchymal stem cells combined with liraglutide relieve acute lung injury through apoptotic signaling restrained by PKA/β-catenin

“…In an in vivo experiment with ALI, we compared the liraglutide alone, three MSCs alone, and combination of liraglutide to observe their repair function. In previous studies, MSCs have been shown to repair ALI [13][14][15][16]19], and liraglutide could alleviate the inflammatory environment of ALI [27][28][29]. In our study, by measuring total protein concentration and cell counts in BALF, wet-to-dry ratio, H&E staining, and lung injury scores, we conclude that liraglutide or MSCs alone and combination of liraglutide could ameliorate the symptoms of ALI.…”

“…They secrete paracrine factors that regulate lung endothelial and epithelial permeability, including growth factors, antimicrobial peptides, and anti-inflammatory cytokines, which could alleviate damaged alveolar fluid clearance, improve lung permeability, and mitigate inflammatory disorders [14][15][16][17][18]. In addition, MSCs are widely available and can be collected from the bone marrow [19], adipose tissues [20], placenta [21], umbilical cord [22], and other tissues [23,24]. However, inflammatory stimulation in the ALI lung microenvironment could lead to a decrease in MSC survival and weaken paracrine capacity [24].…”

Placenta‑derived mesenchymal stem cells ameliorate lipopolysaccharide‑induced inflammation in RAW264.7 cells and acute lung injury in rats

“…The results of the present study demonstrated that pMScs could inhibit the inflammatory response of LPS-induced RAW264.7 macrophage inflammatory model in vitro. in accordance with other previous studies (42)(43)(44), the nc, lPS and lPS + pMSc groups were used both in vitro and in vivo. The effects of pMSc administration without lPS stimulation have not been evaluated in the present study.…”