Modeling alveolar injury using microfluidic co-cultures for monitoring bleomycin-induced epithelial/fibroblastic cross-talk disorder

He, Jun; Chen, Weixing; Deng, Shijie; Xie, Liang; Feng, Juan; Geng, Jing; Jiang, Dechun; Dai, Huaping; Wang, Chen

doi:10.1039/c7ra06752f

Cited by 17 publications

(14 citation statements)

References 39 publications

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“…Lung-on-chip devices have been developed to reflect the exposure of lung to threatening factors (e.g., nanoparticles, 125 drugs, 126 air pollution 127 ) and provide an insight on natural or pathogen (virus and/or bacteria) related lung disorders, 62 leading to a burden in socioeconomic life worldwide. Although there are existing animal models, which enable one to build hypothesis on diagnosis and relevant treatments, it is reported that in many diseases, promising medications have failed in human clinical trials due to toxicity in spite of successful pre-clinical results with animal models.…”

Section: Limitations and Advantagesmentioning

confidence: 99%

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

et al. 2021

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Respiratory viral infections are leading causes of death worldwide. A number of human respiratory viruses circulate in all age groups and adapt to person-to-person transmission. It is vital to understand how these viruses infect the host and how the host responds to prevent infection and onset of disease. Although animal models have been widely used to study disease states, incisive arguments related to poor prediction of patient responses have led to the development of microfluidic organ-on-chip models, which aim to recapitulate organ-level physiology. Over the past decade, human lung chips have been shown to mimic many aspects of the lung function and its complex microenvironment. In this review, we address immunological responses to viral infections and elaborate on human lung airway and alveolus chips reported to model respiratory viral infections and therapeutic interventions. Advances in the field will expedite the development of therapeutics and vaccines for human welfare.

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Section: Limitations and Advantagesmentioning

confidence: 99%

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

et al. 2021

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“…This allows for studying epithelial injury, fibroblast, and macrophage migration under fibrosis. 160 It could be concluded that altering the microenvironment and change in epithelial cross-talk would activate fibroblasts and cause the development of pathological fibroblastic foci.…”

Section: Lungs-on-a-chipmentioning

confidence: 99%

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

Jain,

Shashi Bhushan,

Natarajan

et al. 2024

ACS Biomater. Sci. Eng.

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Fibrosis has been characterized as a global health problem and ranks as one of the primary causes of organ dysfunction. Currently, there is no cure for pulmonary fibrosis, and limited therapeutic options are available due to an inadequate understanding of the disease pathogenesis. The absence of advanced in vitro models replicating dynamic temporal changes observed in the tissue with the progression of the disease is a significant impediment in the development of novel antifibrotic treatments, which has motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends in preparing advanced lung models to recapitulate biochemical and biomechanical processes associated with lung fibrogenesis. We begin by describing the importance of in vivo studies and highlighting the often poor correlation between preclinical research and clinical outcomes and the limitations of conventional cell culture in accurately simulating the 3D tissue microenvironment. Rapid advancement in biomaterials, biofabrication, biomicrofluidics, and related bioengineering techniques are enabling the preparation of in vitro models to reproduce the epithelium structure and operate as reliable drug screening strategies for precise prediction. Improving and understanding these model systems is necessary to find the cross-talks between growing cells and the stage at which myofibroblasts differentiate. These advanced models allow us to utilize the knowledge and identify, characterize, and hand pick medicines beneficial to the human community. The challenges of the current approaches, along with the opportunities for further research with potential for translation in this field, are presented toward developing novel treatments for pulmonary fibrosis.

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“…Pulmonary fibrosis was studied in the co-cultures of A549 alveolar epithelial cells, MRC-5 fibroblasts, and THP-1 macrophages treated with bleomycin in a microfluidic system [85] and in pulmospheres generated from pulmonary fibrosis patients [86]. The pulmospheres can, for instance, be used as a screening system for anti-fibrotic drugs.…”

Section: Cellular Models For Lung Diseasesmentioning

confidence: 99%

Replacement Strategies for Animal Studies in Inhalation Testing

Frőhlich

2021

Sci

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Animal testing is mandatory in drug testing and is the gold standard for toxicity and efficacy evaluations. This situation is expected to change in the future as the 3Rs principle, which stands for the replacement, reduction, and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animal testing have increased. The need to develop and use alternatives depends on the complexity of the research topic and also on the extent to which the currently used animal models can mimic human physiology and/or exposure. The lung morphology and physiology of commonly used animal species differs from that of human lungs, and the realistic inhalation exposure of animals is challenging. In vitro and in silico methods can assess important aspects of the in vivo effects, namely particle deposition, dissolution, action at, and permeation through, the respiratory barrier, and pharmacokinetics. This review discusses the limitations of animal models and exposure systems and proposes in vitro and in silico techniques that could, when used together, reduce or even replace animal testing in inhalation testing in the future.

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Modeling alveolar injury using microfluidic co-cultures for monitoring bleomycin-induced epithelial/fibroblastic cross-talk disorder

Abstract: Epithelial/fibroblastic cross-talk is consider to lead to pulmonary fibrosis, but its pathogenesis remains unclear because no appropriate models allow to visualize the complex disease processes at the human lung epithelial–interstitial interface.

Cited by 17 publications

References 39 publications

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

Human lung-on-chips: Advanced systems for respiratory virus models and assessment of immune response

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

Replacement Strategies for Animal Studies in Inhalation Testing

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