Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Alleviate PM2.5-Induced Lung Injury and Pulmonary Fibrosis

AbstractPulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

Download Full-text

Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential

Cell Communication and Signaling ◽

10.1186/1478-811x-12-26 ◽

2014 ◽

Vol 12 (1) ◽

pp. 26 ◽

Cited By ~ 137

Author(s):

Tatiana Lopatina ◽

Stefania Bruno ◽

Ciro Tetta ◽

Natalia Kalinina ◽

Massimo Porta ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Extracellular Vesicles ◽

Platelet Derived Growth Factor ◽

Angiogenic Potential ◽

Adipose Mesenchymal Stem Cells

Download Full-text

Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury

AJP Cell Physiology ◽

10.1152/ajpcell.00366.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. C234-C244 ◽

Cited By ~ 54

Author(s):

Cong Wang ◽

Huiming Zhu ◽

Zhaorui Sun ◽

Zou Xiang ◽

Yuanyuan Ge ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Injury ◽

Signaling Pathway ◽

Epithelial Differentiation ◽

Unknown Etiology ◽

Alveolar Type ◽

Coculture System

Idiopathic pulmonary fibrosis is a progressive lung disorder of unknown etiology. Previous studies have shown that aberrant activation of the Wnt/β-catenin signaling cascade occurs in lungs of patients with idiopathic pulmonary fibrosis. Given the important roles of the Wnt/β-catenin signaling pathway in the development of pulmonary fibrosis, we targeted this pathway for the intervention of pulmonary fibrosis with XAV939, a small molecule that specifically inhibits Tankyrase 1/2, eventually leading to the degradation of β-catenin and suppression of the Wnt/β-catenin signaling pathway. Our results demonstrated that XAV939 significantly inhibited the activation of Wnt/β-catenin signaling and attenuated bleomycin-induced lung fibrosis in mice, and thus improved the survival of mice with lung injury. Interestingly, previous investigations have confirmed that endogenous and exogenous mesenchymal stem cells could be recruited to the injured lung, although the exact effects of these cells are debatable. To determine the effect of Wnt/β-catenin signaling in the epithelial differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs), we established a coculture system that contains BM-MSCs and alveolar type II epithelial cells. The in vitro experiments demonstrated that XAV939 could promote the differentiation of BM-MSCs into an epithelium-like phenotype in the coculture system. We also found that XAV939 could inhibit the proliferation and myofibroblast differentiation of NIH/3T3 fibroblasts. This work supports that inhibition of the Wnt/β-catenin signaling pathway may be exploited for the treatment of idiopathic pulmonary fibrosis for which effective treatment strategies are still lacking.

Download Full-text