Development of lung tissue models and their applications

Petpiroon, Nalinrat; Netkueakul, Woranan; Sukrak, Kanokwan; Wang, Chen; Liang, Yin; Wang, Mengxue; Liu, Yun; Li, Qiang; Kamran, Rumaisa; Naruse, Keiji; Aueviriyavit, Sasitorn; Takahashi, Ken

doi:10.1016/j.lfs.2023.122208

Cited by 4 publications

(3 citation statements)

References 179 publications

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“…The development of a relevant human lung tissue model is of ultimate importance for method standardization; the in vitro model must have high reproducibility and clinical relevance for inhalation toxicity assessment. However, constructing an in vitro lung tissue model derived from human cells currently remains challenging due to the inherent complexity of the human lung and the number of different cell types involved ( Petpiroon et al, 2023 ).…”

Section: In Vitro Model Systems and High-content Analysismentioning

confidence: 99%

Applying new approach methodologies to assess next-generation tobacco and nicotine products

Thorne,

McHugh,

Simms

et al. 2024

Front. Toxicol.

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In vitro toxicology research has accelerated with the use of in silico, computational approaches and human in vitro tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput in vitro cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing in vivo testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of in vitro tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and “roadmaps” to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate in vitro model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.

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Section: In Vitro Model Systems and High-content Analysismentioning

confidence: 99%

Applying new approach methodologies to assess next-generation tobacco and nicotine products

Thorne,

McHugh,

Simms

et al. 2024

Front. Toxicol.

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“…The limits of this study are as follows: (i) The experiments were only performed in one human lung fibroblast line, and thus similar studies must be repeated in additional cell lines and in cells obtained from patients with different chronic inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease, and various types of lung fibrotic diseases. (ii) The effect of zinc supplementation in the context of lung fibrotic pathologies has to be investigated in future in situ studies in humans, since none of the available animal models of asthma, chronic obstructive pulmonary disease, and fibrosis reflects the full spectrum of the human disease [ 42 , 43 , 44 ]. However, studies in human patients might be limited by ethical aspects related to tissue sampling in diseases that do not require pathological tissue analyses, such as asthma or chronic obstructive pulmonary disease.…”

Section: Discussionmentioning

confidence: 99%

Zinc Iodide Dimethyl Sulfoxide Reduces Collagen Deposition by Increased Matrix Metalloproteinase-2 Expression and Activity in Lung Fibroblasts

Roth,

Han,

S’ng

et al. 2024

Biomedicines

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Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor β1 (TGF-β1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-β1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-β1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.

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“…Moreover, conventional culture methods struggle to replicate the microenvironment and intercellular communication, including direct contact, paracrine signaling, and extracellular vesicle interactions, which are essential for cellular growth and development [4,5]. In recent years, advancements in bio-fabrication, microfluidics, and biosensing have introduced 3D culture models [6][7][8][9]. Currently, two types of 3D culture models are utilized for constructing cardiac microtissues: organoid and heart-on-a-chip models [7,8,10].…”

Section: Introductionmentioning

confidence: 99%

Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells

Liu,

Kamran,

Han

et al. 2023

Preprint

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In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell-cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin toin vivovascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted stronger junction formation between vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The triculture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the biculture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such triculture-derived cardiac tissues exhibited cardiac responses similar toin vivohearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimicsin vivocardiac behavior.

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Development of lung tissue models and their applications

Cited by 4 publications

References 179 publications

Applying new approach methodologies to assess next-generation tobacco and nicotine products

Applying new approach methodologies to assess next-generation tobacco and nicotine products

Zinc Iodide Dimethyl Sulfoxide Reduces Collagen Deposition by Increased Matrix Metalloproteinase-2 Expression and Activity in Lung Fibroblasts

Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells

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