Chip-based liver equivalents for toxicity testing – organotypicalness versus cost-efficient high throughput

Materne, Eva-Maria; Tonevitsky, Alexander G.; Marx, Uwe

doi:10.1039/c3lc50240f

Cited by 100 publications

(88 citation statements)

References 78 publications

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“…these include, for instance, lymphoid tissue to address immunological niches, or they involve the coupling of several organoids in multi-organoid systems. Only two examples are briefly described below to give a perspective on this wide field (Atac et al, 2013;Materne et al, 2013;Schimek et al, 2013;Wagner et al, 2013).…”

Section: Recombinant Human Skin Models (Rhs) For Drug Developmentmentioning

confidence: 99%

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

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Bahinski

Daneshian

et al. 2014

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175

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* a report of t 4 -the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz and Utrecht sponsored by the Doerenkamp-Zbinden Foundation; participants do not represent their institutions and do not necessarily endorse all recommendations made. Summary Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment

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Section: Recombinant Human Skin Models (Rhs) For Drug Developmentmentioning

confidence: 99%

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

Alépée

Bahinski

Daneshian

et al. 2014

ALTEX

175

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“…Both experimental [6,7] and numerical [8,9] researches have been conducted on these applications of micro uidics. A structural form of human liver is composed of sinusoids along which various vital metabolisms occurred.…”

Section: Introductionmentioning

confidence: 99%

A numerical model for predicting hepatocytes ureagenesis and its related inborn enzyme deficiencies: case studies

et al. 2018

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Abstract. One important functionality of liver cells is ammonia detoxi cation and urea production. In this study, a numerical model of the urea cycle in hepatocytes was developed. Navier Stokes and convection equations were employed to study the process of ammonia elimination and urea production using a micro uidic channel. The concentration of urea and ammonia throughout the channel was obtained. Furthermore, the urea cycle was modelled with respect to its four main enzymes. This resulted in twelve rate equations that were solved to determine the concentration of each metabolite participating in the urea cycle. Application of results implied common disorders such as hyperammonemia types I and II and argininosuccinicaciduria types I and II. Result of this study indicated that there is 80% chance of a reduction in concentration of citrulline, argininosuccinate, arginin, carbamoyl phosphate, phosphate and fumarate in hyperammonemia type II. A 10-fold increase of argininosuccinate concentration was observed in both argininosuccinicaciduria types I and II. The predicted result may be useful in better understanding and controlling of metabolite de ciencies in patient abnormalities.

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“…Along this route of about 500 µm, the concentration of oxygen is decreasing because it is being consumed by the cells, and has led to a specialization of the hepatocytes depending on where in the gradient they are located, commonly referred to as liver zonation. For example, most of the albumin and bile is formed in the relatively oxygen-rich zone close to the portal vein while drug metabolism is enhanced at the more oxygendepleted zone close to the central vein [16,52].…”

Section: The Role Of Shear Stress and The Dynamic In Vivo Environmentmentioning

confidence: 99%

“…Such events can lead to the formation of concentration gradients. One example is the oxygen gradient present in the liver (Figure 2.1f) [16]. The liver is supplied with blood from the body via the hepatic portal vein (low oxygen concentration) and the hepatic artery (high oxygen concentration) that move towards the central vein located in the middle of the liver lobule.…”

Section: The Role Of Shear Stress and The Dynamic In Vivo Environmentmentioning

confidence: 99%

“…Organs-on-chips are perfused microdevices inhabited by cells in cultures that mimic the cell's physiological environment [2,[14][15][16][17]. The intention of an organ-on-a-chip is to create a bioanalytical platform where it is possible to study how a cell population reacts to certain chemicals or stimuli in a situation that closely resembles the environment of a certain tissue or organ.…”

Section: The Concept Of Organs-on-chipsmentioning

confidence: 99%

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Organs-on-chips for the pharmaceutical development process: design perspectives and implementations

Christoffersson¹

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Organs-on-chips are dynamic cell culture devices created with the intention to mimic organ function in vitro. Their purpose is to assess the toxicity and efficacy of drugs and, as early as possible in the pharmaceutical development process, predict the outcome of clinical trials. The aim of this thesis is to explain and discuss these cell culture devices from a design perspective and to experimentally exemplify some of the specific functions that characterize organs-on-chips.The cells in our body reside in complex environments with chemical and mechanical cues that affect their function and purpose. Such a complex environment is difficult to recreate in the laboratory and has therefore been overlooked in favor of more simple models, i.e. static twodimensional (2D) cell cultures. Numerous recent reports have shown cell culture systems that can resemble the cell's natural habitat and enhance cell functionality and thereby potentially provide results that better reflects animal and human trials. The way these organs-on-chips improve in vitro cell culture assays is to include e.g. a three-dimensional cell architecture (3D), mechanical stimuli, gradients of oxygen or nutrients, or by combining several relevant cell types that affect each other in close proximity.The research conducted for this thesis shows how cells in 3D spheroids or in 3D hydrogels can be cultured in perfused microbioreactors. Furthermore, a pump based on electroosmosis, and a method for an objective conceptual design process, is introduced to the field of organs-on-chips.Keywords: Organs-on-chips, cell culture models, pharmaceutical development, microfluidics iv v Populärvetenskaplig sammanfattningOrgans-on-chips är modellsystem med avsikt att återskapa ett organs funktion in vitro genom att odla celler från djur eller människor i en omgivning som efterliknar kroppen. Syftet med dessa modeller är att utvärdera ett potentiellt läkemedels toxicitet och effektivitet så tidigt som möjligt i läkemedelsutvecklingen för att kunna förutsäga hur det påverkar människor. Målet med denna avhandling är att förklara och diskutera denna typ av cellmodeller utifrån ett designperspektiv och experimentellt visa några av de specifika funktioner som är en del av konceptet organs-on-chips.Cellerna i våra kroppar befinner sig komplexa miljöer med kemiska och mekaniska signaler som påverkar deras funktion och syfte. Sådana miljöer är svåra att återskapa på laboratoriet och har därför till stor del förbisetts till fördel för enklare modellsystem som ofta består av celler som odlas på plast-eller glasytor under statiska förhållanden. På senare tid har en betydande mängd publikationer visat på att cellmodeller som bättre kan efterlikna cellens naturliga miljö kan förbättra dess olika funktioner och därmed ge resultat som eventuellt kan matcha försöken som görs på djur och människor. Det finns flera olika funktioner, hämtade från vår kunskap om människans biologi, som organs-on-chips kan implementera för att skapa dessa förbättrade cellmiljöer och inkluderar en tre-...

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Chip-based liver equivalents for toxicity testing – organotypicalness versus cost-efficient high throughput

Cited by 100 publications

References 78 publications

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

A numerical model for predicting hepatocytes ureagenesis and its related inborn enzyme deficiencies: case studies

Organs-on-chips for the pharmaceutical development process: design perspectives and implementations

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