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

Abstract

Background 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. 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. Methods We 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. Results We 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. Conclusions Collectively, 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.

Evaluation of the safety and efficacy of using human menstrual blood‐derived mesenchymal stromal cells in treating severe and critically ill COVID‐19 patients: An exploratory clinical trial

“…Supporting information Table S1 includes detailed information on the antibodies used for surface marker analysis. Detection of the differentiation potential of MSCs into the osteogenic differentiation medium, chondrogenic differentiation medium, and adipogenic differentiation medium A and B (Cyagen Biosciences) and their detailed information has been reported in a previous study 66 . PCR analysis was used to check the ACE2 expression level of the MSCs.…”

Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application

“…Levels of inflammation-related cytokines in lung tissue or blood reflect inflammation. Seven studies had evaluated the number of inflammatory cells (namely neutrophils and macrophages) in alveolar lavage fluid, and six of them had found that the number of inflammatory cells was significantly higher in the BLM group than in the control group, being significantly reduced after the MSCs treatment (all p < 0.05) [ 17 , 19 , 23 , 25 , 33 , 34 ], only one study found no significant difference [ 29 ]. Meanwhile, the expression of inflammatory factors in the lung (namely IL-1β, IL-6, and TNF-α) showed the similar trend.…”

“…Meanwhile, the expression of inflammatory factors in the lung (namely IL-1β, IL-6, and TNF-α) showed the similar trend. One study had evaluated the levels of inflammatory cytokines in blood of control group, BLM group and MSCs treatment group, and the results showed that the MSCs treatment could significantly reduce the BLM-induced inflammatory response [ 19 ]. These results suggest a potential immunomodulatory role for MSCs in alleviating pulmonary inflammation.…”

“…The degree of PF was assessed by measuring the content or gene expression of fibrosis-related proteins in lung tissue, including hydroxyproline (HYP), collagen 1α1, and soluble collagen. Thirty studies had evaluated the expression of fibrosis-associated proteins in lung tissue, and twenty-eight of them found that these proteins were significantly increased in the BLM group compared with the control group, being significantly reduced after the MSCs treatment (all p < 0.05) [ 8 – 10 , 12 – 17 , 19 , 21 , 23 – 25 , 28 – 31 , 33 – 40 , 42 , 43 ]. Although there were no significant difference in two studies [ 20 , 22 ].…”

Therapeutic Applications of Mesenchymal Stem Cells in Idiopathic Pulmonary Fibrosis

“…MSCs have been already isolated from a variety of adult and perinatal tissues, including but not limited to bone marrow, adipose tissue, dental pulp, menstrual blood, placenta, amnion, umbilical cord blood, and Wharton’s jelly ( Brown et al, 2019 ; Chen et al, 2020 ). MSCs from different sources exhibit different immunomodulatory abilities, in vitro proliferation properties and in vivo therapeutic functions.…”