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Stem Cell Res Ther. 2018 Nov 14;9(1):311. doi: 10.1186/s13287-018-1045-4.

Bone marrow mesenchymal stromal cells attenuate silica-induced pulmonary fibrosis potentially by attenuating Wnt/β-catenin signaling in rats.

Author information

1
Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, No 18877 Jingshi Road, Lixia District Jinan, Jinan, 250062, Shandong, People's Republic of China.
2
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.
3
Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Brisbane, Queensland, Australia.
4
University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, Queensland, Australia.
5
Department of Radiology, Shandong Tumor Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.
6
Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, No 18877 Jingshi Road, Lixia District Jinan, Jinan, 250062, Shandong, People's Republic of China. duzj1981@163.com.
7
Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, No 18877 Jingshi Road, Lixia District Jinan, Jinan, 250062, Shandong, People's Republic of China. chinashaohua5888@163.com.

Abstract

BACKGROUND:

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. Previous studies have shown that early intervention with bone marrow mesenchymal stem/stromal cells (BMSCs) has positive effect on anti-pulmonary fibrosis caused by silica dust. However, early intervention using BMSCs is not practical, and the therapeutic effects of BMSCs advanced intervention on pulmonary fibrosis have rarely been reported. In this study, we investigated the effects of advanced transplantation (on the 28th day after exposure to silica suspension) of BMSCs on an established rat model of pulmonary fibrosis.

METHODS:

Sprague Dawley (SD) rats were randomly divided into four groups including (1) control group (n = 6) which were normally fed, (2) silica model group (n = 6) which were exposed to silica suspension (1 mL of 50 mg/mL/rat), (3) BMSC transplantation group (n = 6) which received 1 mL BMSC suspension (2 × 106 cells/mL) by tail vein injection on the 28th day after exposure to silica suspension, and (4) BMSC-CM (conditioned medium) transplantation group (n = 6) which received CM from the same cell number by tail vein injection on the 28th day after exposure to silica suspension. On the 56th day after exposure to silica suspension, we used computed tomography (CT), hematoxylin and eosin (H&E), and Masson's trichrome staining to evaluate the changes in lung tissue. We examined the expression of epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related proteins in lung tissue using immunohistochemistry and western blotting.

RESULTS:

Successful construction of a pulmonary fibrosis model was confirmed by H&E and Masson's trichrome staining on the 28th day after exposure to silica suspension. On the 56th day after exposure, pulmonary CT examination showed a relieving effect of BMSCs on silica-induced pulmonary fibrosis which was confirmed by H&E and Masson's trichrome staining. Treatment of BMSCs increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including Vimentin (Vim) and α-Smooth actin (α-SMA) after exposure to silica suspension. Furthermore, we found that Wnt/β-catenin signaling pathway is abnormally activated in silica-induced pulmonary fibrosis, and exogenous transplantation of BMSCs may attenuate their expression.

CONCLUSIONS:

BMSC transplantation inhibits the EMT to alleviate silica-induced pulmonary fibrosis in rats and the anti-fibrotic effect potentially by attenuating Wnt/β-catenin signaling. ᅟ: ᅟ.

KEYWORDS:

Animal model; Bone marrow mesenchymal stem/stromal cells (BMSCs); Cell therapy; Pulmonary fibrosis; Silicosis; Transplantation

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