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Inhalation Toxicology
International Forum for Respiratory Research
Volume 31, 2019 - Issue 2
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Research Article

Mesenchymal stem cell-derived exosomes attenuate phosgene-induced acute lung injury in rats

Ning XuDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
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Yiru ShaoDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
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Kaili YeDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
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Yubei QuDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
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Obulkasim MemetDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaView further author information
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Daikun HeDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaCorrespondence[email protected]
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Jie ShenDepartment of Intensive Care Unit, Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Research Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, China; ;Department of Intensive Care Unit, Medical Center of Radiation Injury, Jinshan Hospital, Fudan University, Shanghai, ChinaCorrespondence[email protected]
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Pages 52-60 | Received 18 Nov 2018, Accepted 05 Mar 2019, Published online: 09 May 2019
 
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Abstract

Objective: We have previously found that mesenchymal stem cell (MSC) therapy can ameliorate phosgene-induced acute lung injury (ALI). Moreover, exosomes can be used as a cell-free alternative therapy. In the present study, we aimed to assess the effect of MSC-derived exosomes on phosgene-induced ALI.

Methods: MSC-derived exosomes were isolated from MSCs through ultracentrifugation. Sprague-Dawley (SD) rats were exposed to phosgene at 8.33 g/m3 for 5 min. MSC-derived exosomes were intratracheally administered and rats were sacrificed at the time points of 6, 24 and 48 h.

Results: Compared with the phosgene group, MSC-derived exosomes reversed respiratory function alterations, showing increased levels of TV, PIF, PEF and EF50 as well as decreased levels of RI and EEP. Furthermore, MSC-derived exosomes improved pathological alterations and reduced wet-to-dry ratio and total protein content in BALF. MSC-derived exosomes reduced the levels of TNF-α, IL-1β and IL-6 and increased the IL-10 level in BALF and plasma. MSC-derived exosomes suppressed the MMP-9 level and increased the SP-C level.

Conclusions: MSC-derived exosomes exerted beneficial effects on phosgene-induced ALI via modulating inflammation, inhibiting MMP-9 synthesis and elevating SP-C level.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by Research project of Shanghai municipal health and Family Planning Commission (No. 201540192) to D. K. H., National Youth Nature Science Foundation of China (No. 81101412) to D. K. H., and National Natural Science Foundation of China (No. 81471850) to S. J.

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