Mesenchymal Stem Cells Attenuate Asthmatic Inflammation and Airway Remodeling by Modulating Macrophages/Monocytes in the IL-13-Overexpressing Mouse Model

Mo, Yosep; Kim, Yujin; Bang, Ji‐Young; Jeong, Jiung; Lee, Chang-Min; Elias, Jack A.; Kang, Hye Ryun

doi:10.4110/in.2022.22.e40

Cited by 6 publications

(3 citation statements)

References 53 publications

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“… 45 Along with Th2 cells, M2 macrophages are a major source of type 2 cytokines that potentiate asthmatic inflammation and airway remodeling that can be attenuated by inhibition of monocytes/macrophages axis. 42 Therefore, higher circulating monocytes in FAO than nFAO group may suggest more recruitment into the airway and differentiation into monocyte-derived macrophages despite the fact that we failed to demonstrate increased sputum macrophage numbers in asthmatics with FAO to a greater extent than nFAO counterpart. However, FAO asthmatics had higher percentage and absolute numbers of airway macrophages with increased airway remodeling activity as demonstrated by TAK1 and p-TAK1 expression than those without FAO.…”

Section: Discussionmentioning

confidence: 59%

“…[39][40][41] Circulating monocytes and airway macrophages play an important role in the development of airway fibrosis in asthma and pulmonary fibrosis. 42,43 Circulating blood monocytes are rapidly recruited to the airway and differentiate into macrophages during asthmatic inflammation; these macrophages are defined as monocyte-derived macrophages. 44 In certain polarizing milieu, they differentiate into M1 and M2 subsets with different phenotypic and functional characteristics.…”

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confidence: 99%

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Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Maneechotesuwan¹,

Wongsurakiat²,

Assawabhumi³

et al. 2023

JAA

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Transforming growth factor-β-associated kinase 1 (TAK1) mediates non-canonical TGF-β signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-β 1 . However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. Patients and Methods: A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-β 1 concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Results: Asthmatic patients with FAO had much greater sputum TGF-β 1 concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-β 1 levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre-and postbronchodilator FEV 1 /FVC ratio. Conclusion: TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact.

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Maneechotesuwan¹,

Wongsurakiat²,

Assawabhumi³

et al. 2023

JAA

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“…We also demonstrated that MSCs significantly decreased not only the total ILC count but also the counts of ILC1s, ILC2s, and ILC3s in the BLM group. To date, only a few studies have reported the effects of MSCs on ILCs, mainly ILC2 [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis

Choi

Bang

et al. 2023

Respir Res

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Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. Methods We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. Results In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. Conclusions Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

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Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

Huang

Zeng

et al. 2023

Cell Transplant

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Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro, and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.

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Mesenchymal Stem Cells Attenuate Asthmatic Inflammation and Airway Remodeling by Modulating Macrophages/Monocytes in the IL-13-Overexpressing Mouse Model

Cited by 6 publications

References 53 publications

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis

Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

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