Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models

Rothbauer, Mario; Rosser, Julie; Zirath, Helene; Ertl, Peter

doi:10.1016/j.copbio.2018.08.009

Cited by 89 publications

(69 citation statements)

References 51 publications

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“…Organ-on-a-chip models attempt to even more accurately mimick the in vivo situation in in vitro models (Van Duinen et al 2015;Ahadian et al 2018;Rothbauer et al 2019). Lung-on-a-chip models were established with alveolar epithelial cells on the apical and endothelial cells on the basolateral side of a porous membrane combined with supply of nutrition by microfluidic flow of medium (Huh et al 2010(Huh et al , 2012Esch et al 2015;Stucki et al 2015).…”

Section: -Dimensional Cultures Cultures At the Air-liquid Interphasmentioning

confidence: 99%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.

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Section: -Dimensional Cultures Cultures At the Air-liquid Interphasmentioning

confidence: 99%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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“…Recent advances in organ-on-a-chip technology have led to state-of-the-art in vitro cell culture systems that include mechanical and functional features present in the human body, resulting in a much better representation of the in vivo microenvironment [6][7][8]. The gut-on-a-chip is an in vitro cell culture system that resembles the dynamic environment of the intestine.…”

Section: Introductionmentioning

confidence: 99%

Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies

et al. 2019

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In oral bioavailability studies, evaluation of the absorption and transport of drugs and food components across the intestinal barrier is crucial. Advances in the field of organ-on-a-chip technology have resulted in a dynamic gut-on-a-chip model that better mimics the in vivo microenvironment of the intestine. Despite a few recent integration attempts, ensuring a biologically relevant microenvironment while coupling with a fully online detection system still represents a major challenge. Herein, we designed an online technique to measure drug permeability and analyse unknown product formation across an intestinal epithelial layer of Caco-2 and HT29-MTX cells cultured on a flow-through Transwell system, while ensuring the quality and relevance of the biological model. Chip-based ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was coupled to the dynamic Transwell system via a series of switching valves, thus allowing alternating measurements of the apical and basolateral sides of the in vitro model. Two trap columns were integrated for online sample pre-treatment and compatibility enhancement. Temporal analysis of the intestinal permeability was successfully demonstrated using verapamil as a model drug and ergotamine epimers as a model for natural toxins present in foods. Evidence was obtained that our newly developed dynamic system provided reliable results versus classical static in vitro models, and moreover, for the first time, epimer-specific transport is shown for ergotamine. Finally, initial experiments with the drug granisetron suggest that metabolic activity can be studied as well, thus highlighting the versatility of the bio-integrated online analysis system developed.

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“…For these reasons, there is a broad need for alternative ways to model human diseases in vitro to accelerate the development of new drugs and advance personalized medicine. In the past 5 years, the development of human organson-a-chips, in which microscale engineering technologies enable the recapitulation of the microarchitecture and functions of living human organs, has opened entirely new possibilities to create in vitro models that reconstitute more complex 3D organ-level structures and to integrate crucial dynamic mechanical cues as well as chemical signals [105].…”

Section: Glomerulus-on-a-chipmentioning

confidence: 99%

Bioengineering strategies for nephrologists: kidney was not built in a day

Peired

Mazzinghi

Chiara

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: The number of patients with end-stage kidney disease is increasing worldwide, creating an unprecedented organ shortage. The kidney is a highly complex structure performing many crucial functions. Dialysis replaces filtration but not all other kidney functions and transplant is limited by kidney availability. Numerous innovative ways are being explored to obtain new kidneys for disease modeling and potentially replace lost kidney functions. Areas covered: In this review, we will go through the different approaches that have been developed over the years to build kidneys. We will first present the current advances in xenotransplantation and generation of interspecies chimeras. Next, we will examine the attempts to create bioengineered kidneys with hemodialysis-derived implantable devices and decellularized organs. Finally, we will examine how organoids and microfluidic devices could answer important pathophysiological questions and model the path toward creating in vitro functional organs, for example through 3D bioprinting. Expert opinion: While all the aforementioned approaches to create new kidneys are promising, their translation into clinical practice seems a long way off, except xenotransplantation. Nonetheless, these novel technologies already consent disease modeling and drug testing at 3D level. We will review the stages of progress toward patient therapy and advantages/drawbacks of the various strategies.

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Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models

Cited by 89 publications

References 51 publications

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Dynamic in vitro intestinal barrier model coupled to chip-based liquid chromatography mass spectrometry for oral bioavailability studies

Bioengineering strategies for nephrologists: kidney was not built in a day

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