Lung-on-a-chip: the future of respiratory disease models and pharmacological studies

Shrestha, Jesus; Bazaz, Sajad Razavi; Es, Hamidreza Aboulkheyr; Azari, Dania Yaghobian; Thierry, Benjamin; Warkiani, Majid Ebrahimi; Ghadiri, Maliheh

doi:10.1080/07388551.2019.1710458

Cited by 139 publications

(82 citation statements)

References 108 publications

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“…]. They offer novel avenues for studying respiratory diseases, for example, intravascular thrombosis, pulmonary edema, inflammation, and more realistic models for pharmaceutical study [ 23 , 56 , 59 , 60 ]. Influenza is a viral infection that attacks the respiratory system.…”

Section: Modeling Viral Diseases In Organ Chipsmentioning

confidence: 99%

Human Organs-on-Chips for Virology

Tang

Abouleila

et al. 2020

Trends in Microbiology

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While conventional in vitro culture systems and animal models have been used to study the pathogenesis of viral infections and to facilitate development of vaccines and therapeutics for viral diseases, models that can accurately recapitulate human responses to infection are still lacking. Human organ-on-a-chip (Organ Chip) microfluidic culture devices that recapitulate tissue–tissue interfaces, fluid flows, mechanical cues, and organ-level physiology have been developed to narrow the gap between in vitro experimental models and human pathophysiology. Here, we describe how recent developments in Organ Chips have enabled re-creation of complex pathophysiological features of human viral infections in vitro .

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Section: Modeling Viral Diseases In Organ Chipsmentioning

confidence: 99%

Human Organs-on-Chips for Virology

Tang

Abouleila

et al. 2020

Trends in Microbiology

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“…The above factors play an important role as physiological indicators of proliferation, contractility, cell motility and tissue morphogenesis. Microflow models are able to accurately map natural conditions; therefore, they show great potential in studying the physiology and etiology of human lung diseases [ 38 ]. Therefore, it seems understandable that in vitro lung and respiratory membrane modeling is a huge challenge for modern tissue engineering.…”

Section: Organs On-a-chipmentioning

confidence: 99%

Novel Strategies in Artificial Organ Development: What Is the Future of Medicine?

Klak¹,

Bryniarski²,

Kowalska³

et al. 2020

Micromachines

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The technology of tissue engineering is a rapidly evolving interdisciplinary field of science that elevates cell-based research from 2D cultures through organoids to whole bionic organs. 3D bioprinting and organ-on-a-chip approaches through generation of three-dimensional cultures at different scales, applied separately or combined, are widely used in basic studies, drug screening and regenerative medicine. They enable analyses of tissue-like conditions that yield much more reliable results than monolayer cell cultures. Annually, millions of animals worldwide are used for preclinical research. Therefore, the rapid assessment of drug efficacy and toxicity in the early stages of preclinical testing can significantly reduce the number of animals, bringing great ethical and financial benefits. In this review, we describe 3D bioprinting techniques and first examples of printed bionic organs. We also present the possibilities of microfluidic systems, based on the latest reports. We demonstrate the pros and cons of both technologies and indicate their use in the future of medicine.

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“…Indeed, not all promising discoveries and treatments obtained from such models have given favorable outcomes with human evidence. Among the reasons behind animal model limitations, the poor standardization of experimental procedures and the variation of environmental conditions as well as interspecies variation (e.g., genetic differences) between animals are listed as the most relevant ( 43 ). In addition, in two-dimensional (2D) culture models, the loss of specific tissue function and physiology leads to a lack of predictability in terms of physiological significance and clinical response prediction ( 44 ).…”

Section: D Cell Cultures As a Research Modelmentioning

confidence: 99%

A 3D Model of Human Trabecular Meshwork for the Research Study of Glaucoma

et al. 2020

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Glaucoma is a multifactorial syndrome in which the development of pro-apoptotic signals are the causes for retinal ganglion cell (RGC) loss. Most of the research progress in the glaucoma field have been based on experimentally inducible glaucoma animal models, which provided results about RGC loss after either the crash of the optic nerve or IOP elevation. In addition, there are genetically modified mouse models (DBA/2J), which make the study of hereditary forms of glaucoma possible. However, these approaches have not been able to identify all the molecular mechanisms characterizing glaucoma, possibly due to the disadvantages and limits related to the use of animals. In fact, the results obtained with small animals (i.e., rodents), which are the most commonly used, are often not aligned with human conditions due to their low degree of similarity with the human eye anatomy. Although the results obtained from non-human primates are in line with human conditions, they are little used for the study of glaucoma and its outcomes at cellular level due to their costs and their poor ease of handling. In this regard, according to at least two of the 3Rs principles, there is a need for reliable human-based in vitro models to better clarify the mechanisms involved in disease progression, and possibly to broaden the scope of the results so far obtained with animal models. The proper selection of an in vitro model with a “closer to in vivo” microenvironment and structure, for instance, allows for the identification of the biomarkers involved in the early stages of glaucoma and contributes to the development of new therapeutic approaches. This review summarizes the most recent findings in the glaucoma field through the use of human two- and three-dimensional cultures. In particular, it focuses on the role of the scaffold and the use of bioreactors in preserving the physiological relevance of in vivo conditions of the human trabecular meshwork cells in three-dimensional cultures. Moreover, data from these studies also highlight the pivotal role of oxidative stress in promoting the production of trabecular meshwork-derived pro-apoptotic signals, which are one of the first marks of trabecular meshwork damage. The resulting loss of barrier function, increase of intraocular pressure, as well the promotion of neuroinflammation and neurodegeneration are listed as the main features of glaucoma. Therefore, a better understanding of the first molecular events, which trigger the glaucoma cascade, allows the identification of new targets for an early neuroprotective therapeutic approach.

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Lung-on-a-chip: the future of respiratory disease models and pharmacological studies

Cited by 139 publications

References 108 publications

Human Organs-on-Chips for Virology

Human Organs-on-Chips for Virology

Novel Strategies in Artificial Organ Development: What Is the Future of Medicine?

A 3D Model of Human Trabecular Meshwork for the Research Study of Glaucoma

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