Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice

Godin, Lindsay M.; Sandri, Brian J; Wagner, Darcy E.; Meyer, Carolyn; Price, Alex; Akinnola, Ifeolu; Weiss, Daniel J.; Panoskaltsis‐Mortari, Angela

doi:10.1371/journal.pone.0150966

Cited by 67 publications

(42 citation statements)

References 53 publications

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“…They showed that fibrotic ECM promotes TGF-β-independent myofibroblast differentiation compared with normal ECM 27. A recent study showed that aged mouse acellular lung matrix induced ECM components (laminin, elastin, fibronectin and collagen) in human bronchial epithelial cells and lung fibroblasts compared with young acellular lung matrix 28. The current study also showed that fibrotic acellular murine lung induces further TGF-β1 release from murine BMMC and PMC.…”

Section: Discussionsupporting

confidence: 63%

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Shimbori

Upagupta

Bellaye

et al. 2019

Thorax

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BackgroundThe role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown.ObjectivesWe investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis.ResultsIn IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%90% vs 60%90% vs FVC<60%, mean difference=−268.6, 95% CI of difference −441.0 to −96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=−17.12, 95% CI of difference −30.02 to −4.22, p=0.006: correlation curves R=−0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BMMC)-DL vs BMMC-TGF-β1 p=0.0005, peritoneal mast cell (PMC)-DL vs PMC-TGF-β1 p=0.0003, total TGF-β1: BMMC-DL vs BMMC-TGF-β1 p=0.013, PMC-DL vs PMC-TGF-β1 p=0.001). Mechanical stretch of lungs caused mast cell degranulation; mast cell stabilisers inhibited degranulation (histamine: cont vs doxantrazole p=0.004, β-hexosaminidase: cont vs doxantrazole, mean difference=1.007, 95% CI of difference 0.2700 to 1.744, p=0.007) and TGF-β1 activation (pSmad2/Smad2: cont vs dox p=0.006). Cromoglycate attenuated pulmonary fibrosis in rats (collagen: phosphate-buffered saline (PBS) vs cromoglycate p=0.036, fibrotic area: PBS vs cromoglycate p=0.031).ConclusionThis study suggests that mast cells may contribute to the progression of pulmonary fibrosis.

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Section: Discussionsupporting

confidence: 63%

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Shimbori

Upagupta

Bellaye

et al. 2019

Thorax

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“…It has been shown that growth on aged ECM leads to significantly lower cellular expression of laminin α3 and α4 chains, which recapitulates the laminin deficiency that is observed in aged lung ECM. These data further highlight the deep biological information that is contained in the lung scaffold, and the feedback loops that exists between reparative cell populations and the underlying protein matrix (8). …”

Section: Introductionmentioning

confidence: 75%

Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration

Gilpin

Evangelista-Leite

et al. 2017

Biomaterials

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Organ engineering based on native matrix scaffolds involves combining regenerative cell populations with corresponding biological matrices to form functional grafts on-demand. The extracellular matrix (ECM) that is retained following lung decellularization provides essential structure and biophysical cues for whole organ regeneration after recellularization. The unique ECM composition in the early post-natal lung, during active alveologenesis, may possess distinct signals that aid in driving cell adhesion, survival, and proliferation. We evaluated the behavior of basal epithelial stem cells (BESCs) isolated from adult human lung tissue, when cultured on acellular ECM derived from neonatal (aged < 1 week) or adult lung donors (n=3 donors per group). A significant difference in cell proliferation and survival was found. We next performed in-depth proteomic analysis of the lung scaffolds to quantify proteins significantly enriched in the neonatal ECM, and identified the glycoproteins Fibrillin-2 (FBN-2) and Tenascin-C (TN-C) as potential mediators of the observed effect. BESCs cultured on Collagen Type IV coated plates, supplemented with FBN-2 and TN-C demonstrated significantly increased proliferation and decreased cellular senescence. No significant increase in epithelial-to-mesenchymal transition was observed. In vitro migration was also increased by FBN-2 and TN-C treatment. Decellularized lung scaffolds treated with FBN-2 and TN-C prior to re-epithelialization supported greater epithelial proliferation and tissue remodeling. BESC distribution, matrix alignment, and overall tissue morphology was improved on treated lung scaffolds, after 3 and 7 days of ex vivo lung culture. These results demonstrate that scaffold re-epithelialization is enhanced on neonatal lung ECM, and that supplementation of FBN-2 and TN-C to the native scaffold may be a valuable tool in lung tissue regeneration.

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“…Previous studies have indicated that 1) ECM retention after decellularization is higher in younger tissues, and 2) de novo matrix production and cell proliferation is increased after recellularization using younger rather than older tissues (52, 53). Taken together, these previous works predict that in the absence of species-specific cell-matrix interactions, our human ECs should perform better on rat and pig (younger) tissues rather than primate and human (older) tissues.…”

Section: Discussionmentioning

confidence: 99%

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine

et al. 2016

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Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration.

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Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice

Cited by 67 publications

References 53 publications

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration

Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine

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