Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibros
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RESEARCH
Open Access
Exosomes derived from three-dimensional cultured human umbilical cord mesenchymal stem cells ameliorate pulmonary fibrosis in a mouse silicosis model Chunjie Xu1,2, Jing Zhao1,2, Qiuyue Li1,2, Lin Hou1,2, Yan Wang1,2, Siling Li1,2, Fuyang Jiang1,2, Zhonghui Zhu1,2* and Lin Tian1,2*
Abstract Background: Silicosis is an occupational respiratory disease caused by long-term excessive silica inhalation, which is most commonly encountered in industrial settings. Unfortunately, there is no effective therapy to delay and cure the progress of silicosis. In the recent years, stem cell therapy has emerged as an attractive tool against pulmonary fibrosis (PF) owing to its unique biological characteristics. However, the direct use of stem cells remains limitation by many risk factors for therapeutic purposes. The exclusive utility of exosomes secreted from stem cells, rather than cells, has been considered a promising alternative to overcome the limitations of cell-based therapy while maintaining its advantages. Methods and results: In this study, we first employed a three-dimensional (3D) dynamic system to culture human umbilical cord mesenchymal stem cell (hucMSC) spheroids in a microcarrier suspension to yield exosomes from serum-free media. Experimental silicosis was induced in C57BL/6J mice by intratracheal instillation of a silica suspension, with/without exosomes derived from hucMSC (hucMSC-Exos), injection via the tail vein afterwards. The results showed that the gene expression of collagen I (COL1A1) and fibronectin (FN) was upregulated in the silica group as compared to that in the control group; however, this change decreased with hucMSC-Exo treatment. The value of FEV0.1 decreased in the silica group as compared to that in the control group, and this change diminished with hucMSC-Exo treatment. These findings suggested that hucMSC-Exos could inhibit silica-induced PF and regulate pulmonary function. We also performed in vitro experiments to confirm these findings; the results revealed that hucMSC-Exos decreased collagen deposition in NIH-3T3 cells exposed to silica. Conclusions: Taken together, these studies support a potential role for hucMSC-Exos in ameliorating pulmonary fibrosis and provide new evidence for improving clinical treatment induced by silica. Keywords: Silicosis, Pulmonary fibrosis, 3D, hucMSC-Exos
* Correspondence: [email protected]; [email protected] 1 Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, No. 10, Xitoutiao Youanmen Street, Beijing 100069, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or ot
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