Targeted migration of bone marrow mesenchymal stem cells inhibits silica-induced pulmonary fibrosis in rats.

Abstract

BACKGROUND:

Silicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis. We demonstrated an anti-fibrotic effect of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung fibrosis. In the present study, we sought to clarify the homing ability of BMSCs and the specific mechanisms for their effects.

METHODS AND RESULTS:

The biodistribution of BMSCs was identified by near-infrared fluorescence (NIRF) imaging in vivo and in vitro. The results showed that BMSCs labeled with NIR-DiR dyes targeted silica-injured lung tissue, wherein they reached a peak at 6 h post-injection and declined dramatically by day 3. Based on these findings, a second injection of BMSCs was administered 3 days after the first injection. The injected BMSCs migrated to the injured lungs, but did not undergo transformation into specific lung cell types. Interestingly, the injection of BMSC-conditioned medium (BMSCs-CM) significantly attenuated silica-induced pulmonary fibrosis. The collagen deposition and number of nodules were decreased in lung tissues of BMSCs-CM-treated rats. In parallel with these findings, the mRNA levels of collagen I, collagen III, and fibronectin, and the content of transforming growth factor (TGF)-β1 and hydroxyproline were decreased in the BMSCs-CM-treated group compared with the silica group. In addition, alveolar epithelial markers were upregulated by BMSCs-CM treatment.

CONCLUSIONS:

BMSCs migrated to injured areas of the lung after silica instillation and attenuated pulmonary fibrosis. The anti-fibrotic effects of BMSCs were mainly exerted in paracrine manner, rather than through their ability to undergo differentiation.

• Authors: Xiaoli Li, Guoliang An, Yan Wang, Di Liang, Zhonghui Zhu, Lin Tian
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 9 Issue 1 Pg. 335 (12 04 2018) ISSN: 1757-6512 [Electronic] England
• PMID: 30514375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbocyanines
• Culture Media, Conditioned
• indotricarbocyanine
• Silicon Dioxide

Topics

• Animals
• Bone Marrow Cells (cytology, drug effects, metabolism)
• Carbocyanines (chemistry)
• Cell Death (drug effects)
• Cell Movement (drug effects)
• Culture Media, Conditioned (pharmacology)
• Epithelial Cells (drug effects, pathology)
• Female
• Gene Expression Regulation (drug effects)
• Lung (pathology)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Models, Biological
• Phenotype
• Pulmonary Fibrosis (chemically induced, genetics, prevention & control)
• Rats, Wistar
• Silicon Dioxide