Human menstrual blood-derived stem cells mitigate bleomycin-induced pulmonary fibrosis through anti-apoptosis and anti-inflammatory effects

Xin Chen,Charlie Xiang,Yanling Wang,Yi Wu,Wendi Zheng,Li Yuan,Yifei Li,Sining Zhou,Lijun Chen,Huikang Xu

doi:10.1186/s13287-020-01926-x

Abstract

BackgroundIdiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis.MethodsWe investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro.ResultsWe observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR.ConclusionsCollectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.

Highlights

Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate
mesenchymal stem cells (MenSCs) reduce BLM-induced apoptosis and epithelial-mesenchymal transition (EMT) of MLE12 cells We measured the biological effect of MenSCs on the proliferation of murine lung epithelia-12 (MLE-12) cells, with cell counting kit-8 (CCK8) assay results showing that MenSCs significantly reduced BLMinduced MLE-12 cell injury (Fig. 2a) and promoted their clonogenic potential compared with the BLM group (Fig. 2b)
These results indicate that MenSCs have an anti-apoptosis effect on the proliferation of MLE-12 cells treated with BLM

Summary

Introduction

Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis is a fatal interstitial lung disease which is characterized by fibroblast proliferation and extracellular matrix formation, and accompanied by inflammatory lesions and structural damage. Lung transplantation is the optimal option to improve the survival rate and quality of life of pulmonary fibrosis patients. This option is limited due to a lack of donors [4]. With the development of cell-based therapy, stem cells have become a promising choice for treating a series of diseases

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