PMID- 30867053 OWN - NLM STAT- MEDLINE DCOM- 20200422 LR - 20200422 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 10 IP - 1 DP - 2019 Mar 12 TI - The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard. PG - 90 LID - 10.1186/s13287-019-1189-x [doi] LID - 90 AB - BACKGROUND: Sulfur 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. METHODS: Mice 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. RESULTS: Fluorescence 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. CONCLUSION: BMSCs 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. FAU - Feng, Yongwei AU - Feng Y AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Xu, Qingqiang AU - Xu Q AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Yang, Yuyan AU - Yang Y AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Shi, Wenwen AU - Shi W AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Meng, Wenqi AU - Meng W AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Zhang, Hao AU - Zhang H AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - He, Xiaowen AU - He X AD - Origincell Technology Group Co., Ltd., 1118 Halei Rd, Shanghai, 201203, China. FAU - Sun, Mingxue AU - Sun M AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Chen, Yongchun AU - Chen Y AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Zhao, Jie AU - Zhao J AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. FAU - Guo, Zhenhong AU - Guo Z AD - National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China. guozh@immunol.org. FAU - Xiao, Kai AU - Xiao K AD - Lab of Toxicology and Pharmacology, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, China. kaixiaocn@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190312 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - T8KEC9FH9P (Mustard Gas) SB - IM MH - *Acute Lung Injury/chemically induced/immunology/pathology/therapy MH - Animals MH - Bone Marrow Cells/*immunology/pathology MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*immunology/pathology MH - Mice MH - Mice, Inbred ICR MH - Mustard Gas/*toxicity PMC - PMC6416968 OTO - NOTNLM OT - Acute lung injury OT - Anti-inflammation OT - Bone marrow-derived mesenchymal stromal cell OT - Immunomodulation OT - Sulfur mustard OT - Tissue repair COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Under the permission of the Ethical Review Board of Second Military Medical University. All animal experiments were approved and conformed to the guidelines set by the Institutional Animal Care and Use of Second Military Medical University. CONSENT FOR PUBLICATION: All authors have reviewed the manuscript and approved the publication. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/03/15 06:00 MHDA- 2020/04/23 06:00 PMCR- 2019/03/12 CRDT- 2019/03/15 06:00 PHST- 2018/08/06 00:00 [received] PHST- 2019/02/25 00:00 [accepted] PHST- 2019/01/11 00:00 [revised] PHST- 2019/03/15 06:00 [entrez] PHST- 2019/03/15 06:00 [pubmed] PHST- 2020/04/23 06:00 [medline] PHST- 2019/03/12 00:00 [pmc-release] AID - 10.1186/s13287-019-1189-x [pii] AID - 1189 [pii] AID - 10.1186/s13287-019-1189-x [doi] PST - epublish SO - Stem Cell Res Ther. 2019 Mar 12;10(1):90. doi: 10.1186/s13287-019-1189-x.