Chronic asthma and Mesenchymal stem cells: Hyaluronan and airway remodeling

Abstract

BackgroundPrevious studies have demonstrated that ovalbumin sensitization promotes chronic asthma phenotype in murine asthma model. Human mesenchymal stem cells (hMSCs) are multipotent cells in vitro that have been shown to decrease inflammation and can reverse airway remodeling when infused into an in vivo chronic asthma model. However, the mechanism by which hMSCs reverse remodeling is still unclear. In this study, we hypothesized that hMSCs influence remodeling by decreasing extracellular matrix (ECM) deposition, more specifically by decreasing collagen I, collagen III, and hyaluronan synthesis.MethodsChronic asthma phenotype was produced in an in vitro model with 3 T3 murine airway fibroblast cells by stimulating with GM-CSF. Collagen I and collagen III gene expression was investigated using RT-PCR and Taqman techniques. Hyaluronan was evaluated using FACE and Western Blots. The chronic asthma phenotype was produced in vivo in murine model using sensitization with ovalbumin with and without hMSC infusion therapy. ECM deposition (specifically trichrome staining, soluble and insoluble collagen deposition, and hyaluronan production) was evaluated. Image quantification was used to monitor trichrome staining changes.ResultsGM-CSF which induced collagen I and collagen III production was down-regulated with hMSC using co-culture. In the in vivo model, Ovalbumin induced enhanced ECM deposition, soluble and insoluble collagen production, and lung elastance. hMSC infusions decreased ECM deposition as evidenced by decreases in soluble and insoluble collagen production.ConclusionhMSCs participate in improved outcomes of remodeling by reversing excess collagen deposition and changing hyaluronan levels.

Unraveling the therapeutic effects of mesenchymal stem cells in asthma

“…Systemic injection of human bone marrow MSCs via tail vein induced pulmonary macrophage polarization toward M2 type via the promotion of the TGF-β/Smad signaling pathway [116]. Interestingly, xenogeneic transplantation of human MSC retro-orbital administration in mice diminished the hyaluronan mucus in the chronic asthma model [32]. These findings support the assumption that autologous, allogeneic, and xenogeneic transplantation of MSCs could promote anti-inflammatory outcomes via engaging different mechanisms.…”

Variable Expressed Methylation Sites of Aging-related Genes in Asthma

“…Of particular note is the potential role of aging in the parthenogenesis of asthma [28,29]. Many studies have demonstrated the exist of aging structural cells, immune cells and mesenchymal cells in asthmatic lung although the speci c role of aging cells in asthma is still not fully understood [20,30,31]. Meanwhile, some related studies have also con rmed the different expression of aging-related genes (such as TP53 and FOXO3) in the development of respiratory diseases [32,33].…”

Casticin alleviates lipopolysaccharide‐induced inflammatory responses and expression of mucus and extracellular matrix in human airway epithelial cells through Nrf2/Keap1 and NF‐κB pathways

“…Airway remodeling and inflammation in asthma are dependent on the ECM proteins, such as collagens and fibronectin (Liu et al, ). However, airway remodeling with excessive deposition of ECM is correlated with increased airway responsiveness and asthma severity (Goldstein, Lauer, Caplan, & Bonfield, ). In the present study, we found that casticin inhibited LPS‐induced expression of MUC5AC and deposition of ECM including collagen type I and fibronectin in 16‐HBE cells.…”

“…Airway remodeling and inflammation in asthma are dependent on the ECM proteins, such as collagens and fibronectin . However, airway remodeling with excessive deposition of ECM is correlated with increased airway responsiveness and asthma severity (Goldstein, Lauer, Caplan, & Bonfield, 2017).…”