Differentiation of Mesenchymal Multipotent Stromal Cells of the Lungs in Pneumofibrosis

Скурихин, Е. Г.; Khmelevskaya, E. S.; Першина, О. В.; Ермакова, Н. Н.; Krupin, V. A.; Reztsova, A. M.; Ермолаева, Л. А.; Yakushina, V. D.; Степанова, И. Э.; Reztsova, V. M.; Чердынцева, Н. В.; Стахеева, М. Н.; Дыгай, А. М.

doi:10.1007/s10517-013-1995-6

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…While historically the inflammatory processes were thought to trigger and facilitate the development of IPF 1 , this view was questioned for the ineffectiveness of anti-inflammatory therapy in IPF 2 , 37 . Recently, a major key pathophysiological event in IPF that was under discussion was repetitive injury without appropriate repair and subsequent myofibroblast differentiation of MSCs 38 . Our observations in vivo proved that LR-MSCs (Sca-1 + ) could differentiate into myofibroblasts (α-SMA + ) in BLM-induced pulmonary fibrosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix production, impairing function and contributing to pulmonary fibrosis. Hedgehog and Wnt signaling are developmental signal cascades that play an essential role in regulating embryogenesis and tissue homeostasis. Recently, it has been reported that both hedgehog and Wnt signaling play important roles in pulmonary fibrogenesis. Thus, the identification of specific target regulators may yield new strategy for pulmonary fibrosis therapies. In our work, we demonstrated the critical role of Gli1, Wnt7b, Wnt10a and Fzd10 in the process of pulmonary fibrogenesis in vitro and in vivo. Gli1 was induced in LR-MSCs following TGF-β1 treatment and fibrotic lung tissues. Inhibition of Gli1 suppressed myofibroblast differentiation of LR-MSCs and pulmonary fibrosis, and decreased the expression of Wnt7b, Wnt10a and β-catenin. Gli1 bound to and increased promoter activity of the Wnt7b and Wnt10a genes, and Wnt7b and Wnt10a were critical activators of Wnt/β-catenin signaling. It was noteworthy that Fzd10 knockdown reduced Wnt7b and Wnt10a-induced activation of Wnt/β-catenin signaling, which imply that Wnt7b and Wnt10a may be the ligands for Fzd10. Moreover, siRNA-mediated inhibition of Fzd10 prevented TGF-β1-induced myofibroblast differentiation of LR-MSCs in vitro and impaired bleomycin-induced pulmonary fibrosis. We conclude that hedgehog and Wnt/β-catenin signaling play a critical role in promoting myofibroblast differentiation of LR-MSCs and development of pulmonary fibrosis. These findings elucidate a therapeutic approach to attenuate pulmonary fibrosis through targeted inhibition of Gli1 or Fzd10.

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Section: Discussionmentioning

confidence: 99%

The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis

et al. 2018

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“…MSCs, which were administered to mice during the fibrotic stage of radiation-induced PF model, differentiated into fibroblast-like phenotype and aggravated the fibrotic lesion [ 92 ]. MSCs isolated from BLM-injured mice lungs were also more likely to differentiate into fibroblasts in vitro [ 93 ] (Figure 2 ).…”

Section: Roles and Mechanisms Of Mscs In Pulmonary Fibrosismentioning

confidence: 99%

Mesenchymal stem cells in idiopathic pulmonary fibrosis

Yue

Luo

2017

Oncotarget

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Idiopathic pulmonary fibrosis (IPF) is a major cause of respiratory failure in critically ill patients and common outcome of various lung interstitial diseases. Its mortality remains high, and no effective pharmacotherapy, in addition to artificial ventilation and transplantation, exists. As such, the administration of mesenchymal stem or stromal cells (MSCs) is currently investigated as a new therapeutic method for pulmonary fibrosis. Clinical trials on MSC-based therapy as a potential treatment for lung injury and fibrosis are also performed. MSCs can migrate to injured sites and secrete multiple paracrine factors and then regulate endothelial and epithelial permeability, decrease inflammation, enhance tissue repair, and inhibit bacterial growth. In this review, recent studies on stem cells, particularly MSCs, involved in alleviating lung inflammation and fibrosis and their potential MSC-induced mechanisms, including migration and differentiation, soluble factor and extracellular vesicle secretion, and endogenous regulatory functions, were summarized.

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“…Furthermore, Marriott et al identified a subpopulation of MSCs expressing ABCG2 that contribute to fibrotic remodeling [35]. MSCs isolated from lungs of mice injured by bleomycin were also more likely to differentiate, in vitro, into fibroblasts [36].…”

Section: Contribution To Fibrosismentioning

confidence: 99%

Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review

Srour

Thébaud

2015

Stem Cells Translational Medicine

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Data from 17 animal studies indicated mesenchymal stromal cell (MSC) therapy led to improvement in bleomycin‐induced lung collagen deposition, pulmonary fibrosis Ashcroft score (in most studies), histopathology, 14‐day survival in animal models, and reduced levels of markers of inflammation. Preclinical data offer better support for human trials of MSCs in acute exacerbations rather than the chronic phase of pulmonary fibrosis.

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Differentiation of Mesenchymal Multipotent Stromal Cells of the Lungs in Pneumofibrosis

Cited by 4 publications

References 14 publications

The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis

The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis

Mesenchymal stem cells in idiopathic pulmonary fibrosis

Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review

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