Mesenchymal Stem Cells for the Treatment of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is an interstitial disease of unknown etiology characterized by progressive pulmonary fibrosis. Pirfenidone and nintedanib are the only drugs that can prolong the time to disease progression, slow down the decline in lung function, and prolong survival. However, they do not offer a cure and are associated with tolerability issues. The pluripotency of mesenchymal stem cells (MSCs) and their ability to regulate immunity, inhibit inflammation, and promote epithelial tissue repair highlight the promise of MSC therapy for treating interstitial lung disease. However, optimal protocols are lacking for multi-parameter selection in MSC therapy. This review summarizes preclinical studies on MSC transplantation for the treatment of interstitial lung disease and clinical studies with known results. An analysis of relevant factors for the optimization of treatment plans is presented, including MSCs with different sources, administration routes and timing, dosages, frequencies, and pretreatments with MSCs. This review proposes an optimized plan for guiding the design of future clinical research to identify therapeutic options for this complex disease.

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LSC - 2021 - Role of mitochondrial function of lung mesenchymal stem cells in idiopathic pulmonary fibrosis

10.1183/13993003.congress-2021.pa3695 ◽

2021 ◽

Author(s):

Truyols Joan ◽

Aina Martin ◽

Andreas Jahn ◽

Carlos Rio ◽

Ernest Sala ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Mitochondrial Function

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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.

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How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis

International Journal of Molecular Sciences ◽

10.3390/ijms21218140 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8140

Author(s):

Martina Bonifazi ◽

Mariangela Di Vincenzo ◽

Miriam Caffarini ◽

Federico Mei ◽

Michele Salati ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chronic Disease ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Cell Types ◽

And Control ◽

And Oxidative Stress

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by fibroblasts activation, ECM accumulation, and diffused alveolar inflammation. The role of inflammation in IPF is still controversial and its involvement may follow nontraditional mechanisms. It is seen that a pathological microenvironment may affect cells, in particular mesenchymal stem cells (MSCs) that may be able to sustain the inflamed microenvironment and influence the surrounding cells. Here MSCs have been isolated from fibrotic (IPF-MSCs) and control (C-MSCs) lung tissue; first cells were characterized and compared by the expression of molecules related to ECM, inflammation, and other interdependent pathways such as hypoxia and oxidative stress. Subsequently, MSCs were co-cultured between them and with NHLF to test the effects of the cellular crosstalk. Results showed that pathological microenvironment modified the features of MSCs: IPF-MSCs, compared to C-MSCs, express higher level of molecules related to ECM, inflammation, oxidative stress, and hypoxia; notably, when co-cultured with C-MSCs and NHLF, IPF-MSCs are able to induce a pathological phenotype on the surrounding cell types. In conclusion, in IPF the pathological microenvironment affects MSCs that in turn can modulate the behavior of other cell types favoring the progression of IPF.

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