A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses

2011 ◽  
Vol 6 (6) ◽  
pp. 065002 ◽  
Author(s):  
Hui Pan ◽  
Hongliang Jiang ◽  
Sarah Kantharia ◽  
Weiliam Chen
Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 631
Author(s):  
Luis Soriano ◽  
Tehreem Khalid ◽  
Fergal J. O'Brien ◽  
Cian O'Leary ◽  
Sally-Ann Cryan

Translation of novel inhalable therapies for respiratory diseases is hampered due to the lack of in vitro cell models that reflect the complexity of native tissue, resulting in many novel drugs and formulations failing to progress beyond preclinical assessments. The development of physiologically-representative tracheobronchial tissue analogues has the potential to improve the translation of new treatments by more accurately reflecting in vivo respiratory pharmacological and toxicological responses. Herein, advanced tissue-engineered collagen hyaluronic acid bilayered scaffolds (CHyA-B) previously developed within our group were used to evaluate bacterial and drug-induced toxicity and inflammation for the first time. Calu-3 bronchial epithelial cells and Wi38 lung fibroblasts were grown on either CHyA-B scaffolds (3D) or Transwell® inserts (2D) under air liquid interface (ALI) conditions. Toxicological and inflammatory responses from epithelial monocultures and co-cultures grown in 2D or 3D were compared, using lipopolysaccharide (LPS) and bleomycin challenges to induce bacterial and drug responses in vitro. The 3D in vitro model exhibited significant epithelial barrier formation that was maintained upon introduction of co-culture conditions. Barrier integrity showed differential recovery in CHyA-B and Transwell® epithelial cultures. Basolateral secretion of pro-inflammatory cytokines to bacterial challenge was found to be higher from cells grown in 3D compared to 2D. In addition, higher cytotoxicity and increased basolateral levels of cytokines were detected when epithelial cultures grown in 3D were challenged with bleomycin. CHyA-B scaffolds support the growth and differentiation of bronchial epithelial cells in a 3D co-culture model with different transepithelial resistance in comparison to the same co-cultures grown on Transwell® inserts. Epithelial cultures in an extracellular matrix like environment show distinct responses in cytokine release and metabolic activity compared to 2D polarised models, which better mimic in vivo response to toxic and inflammatory stimuli offering an innovative in vitro platform for respiratory drug development.


2019 ◽  
Vol 305 ◽  
pp. 110-116 ◽  
Author(s):  
Min Jeong Gu ◽  
Seung Eun Han ◽  
Kyoryen Hwang ◽  
Elisabeth Mayer ◽  
Nicole Reisinger ◽  
...  

Author(s):  
Alison Hill ◽  
Jessica Donaldson ◽  
Cornelia Blume ◽  
Liku Tezera ◽  
Hitasha Rupani ◽  
...  

Author(s):  
Aya Kakinoki ◽  
Tsuyoshi Kameo ◽  
Shoko Yamashita ◽  
Kazuyuki Furuta ◽  
Satoshi Tanaka

Accumulating evidence suggests that mast cells should play critical roles in disruption and maintenance of intestinal homeostasis, although it remains unknown how they affect local microenvironment. Interleukin-9 (IL-9) was found to play critical roles in intestinal mast cell accumulation induced in various pathological conditions, such as parasite infection and oral allergen-induced anaphylaxis. Newly recruited intestinal mast cells trigger inflammatory responses and damage epithelial integrity through release of a wide variety of mediators including mast cell proteases. We established a novel culture model (mucosal mast cell-like cultured mast cells, MMC-like MCs), in which murine IL-3-dependent bone marrow-derived cultured mast cells (BMMCs) were further cultured in the presence of stem cell factor and IL-9. In MMC-like MCs, drastic up-regulation of Mcpt1 and Mcpt2 was found. Although histamine storage and tryptase activity were significantly downregulated in the presence of SCF and IL-9, it was entirely reversed when mast cells were co-cultured with a murine fibroblastic cell line, Swiss 3T3. MMC-like MCs underwent degranulation upon IgE-mediated antigen stimulation, which was found to less sensitive to lower concentrations of IgE in comparison with BMMCs. This model might be useful for investigation of the spatiotemporal changes of newly recruited intestinal mast cells.


Thorax ◽  
2014 ◽  
Vol 69 (Suppl 2) ◽  
pp. A49-A49
Author(s):  
A. Hill ◽  
L. Tezera ◽  
C. Blume ◽  
C. Grainge ◽  
D. Davies ◽  
...  

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 428 ◽  
Author(s):  
Qian Jiang ◽  
Hua Zhang ◽  
Runqiang Yang ◽  
Qianru Hui ◽  
Yuhuan Chen ◽  
...  

Red-osier dogwood extracts (RDE) contain high levels of phenolic compounds which have been recognized as natural antioxidants. In this study, the potential of RDE to prevent cardiovascular diseases (CVDs) was evaluated using Caco-2 cells and a co-culture model of Caco-2 BBe1/EA.hy926 cells in Transwell® plates. The results showed that RDE supplementation significantly prevented interleukin-8 (IL-8) production and suppressed the gene expression of IL-8, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and cyclooxygenase 2 (COX-2) in the TNF-α inflamed Caco-2 cells. Meanwhile, the polyphenols (quercetin-3-glucoside, quercetin-glucuronide, rutin, quercetin-3-O-malonylglucoside, and kaempferol-glucoside) in the RDE were validated to be absorbed by Caco-2 BBe1 cells and transported to the basal chamber where EA.hy926 cells were located during 12 h incubation. The transported polyphenols were able to prevent IL-8 production and suppress the gene expression of proinflammatory mediators (TNF-α, ICAM-1, VCAM-1, and COX-2) in the TNF-α or oxidized low-density lipoprotein (ox-LDL) treated EA.hy926 cells. These novel findings demonstrated that phenolic compounds in RDE can be transported to the cardiovascular system by intestinal absorption and mitigate the inflammatory responses of vascular endothelial cells, indicating that RDE could be a natural resource of polyphenols to prevent inflammation cytokine or oxidized lipid-induced CVDs.


2019 ◽  
Vol 21 (1) ◽  
pp. 236 ◽  
Author(s):  
Aya Kakinoki ◽  
Tsuyoshi Kameo ◽  
Shoko Yamashita ◽  
Kazuyuki Furuta ◽  
Satoshi Tanaka

Accumulating evidence suggests that mast cells play critical roles in disruption and maintenance of intestinal homeostasis, although it remains unknown how they affect the local microenvironment. Interleukin-9 (IL-9) was found to play critical roles in intestinal mast cell accumulation induced in various pathological conditions, such as parasite infection and oral allergen-induced anaphylaxis. Newly recruited intestinal mast cells trigger inflammatory responses and damage epithelial integrity through release of a wide variety of mediators including mast cell proteases. We established a novel culture model (IL-9-modified mast cells, MCs/IL-9), in which murine IL-3-dependent bone-marrow-derived cultured mast cells (BMMCs) were further cultured in the presence of stem cell factor and IL-9. In MCs/IL-9, drastic upregulation of Mcpt1 and Mcpt2 was found. Although histamine storage and tryptase activity were significantly downregulated in the presence of SCF and IL-9, this was entirely reversed when mast cells were cocultured with a murine fibroblastic cell line, Swiss 3T3. MCs/IL-9 underwent degranulation upon IgE-mediated antigen stimulation, which was found to less sensitive to lower concentrations of IgE in comparison with BMMCs. This model might be useful for investigation of the spatiotemporal changes of newly recruited intestinal mast cells.


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