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Donkers, J.M. (author), van der Vaart, J.I. (author), van de Steeg, E. (author)The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, the characterization of intestinal disease processes is increasingly gaining more attention, as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of...article 2023
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Agamennone, V. (author), van den Broek, T.J. (author), de Kat Angelino-Bart, A. (author), Hoevenaars, F.P.M. (author), van der Kamp, J.W. (author), Schuren, F.H.J. (author)The development of microbiome-targeted strategies is limited by individual differences in gut microbiome composition and metabolic responses to interventions. In vitro models that can replicate this variation allow us to conduct pre-clinical studies and assess efficacy. This study describes the exposure of 16 individual fecal microbiota samples...article 2023
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Wiese, M. (author), Schuren, F.H.J. (author), Smits, W.K. (author), Kuijpers, E.J. (author), Ouwens, A. (author), Heerikhuisen, M. (author), Vigsnaes, L. (author), van den Broek, T.J. (author), de Boer, P. (author), Montijn, R.C. (author), Vossen, J.M.B.M. (author)Background: Clostridioides difficile is a Gram-positive anaerobic bacterium that can produce the toxins TcdA and/or TcdB and is considered an opportunistic pathogen. C. difficile is mainly transmitted as endospores, which germinate to produce the pathogenic vegetative cells under suitable conditions in the gut. To efficiently screen novel...article 2022
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Suchowerska, A.K. (author), Stokman, G. (author), Palmer, J.T. (author), Coghlan, P.A. (author), Pieterman, E.J. (author), Keijzer, N. (author), Lambert, G. (author), Chemello, K. (author), Jaafar, A.K. (author), Parmar, J. (author), Yan, L. (author), Tong, Y. (author), Mu, L. (author), Princen, H.M.G. (author), Bonnar, J. (author), Evison, B.J. (author)Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...article 2022
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Fragki, S. (author), Piersma, A.H. (author), Westerhout, J. (author), Kienhuis, A. (author), Kramer, N.I. (author), Zeilmaker, M.J. (author)Toxicology is moving away from animal testing towards in vitro tools to assess chemical safety. This new testing framework requires a quantitative method, i.e. kinetic modelling, which extrapolates effective concentrations in vitro to a bioequivalent human dose in vivo and which can be applied on “high throughput screening” of a wide variety of...article 2022
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Donkers, J.M. (author), Hoppener, E.M. (author), Grigoriev, I. (author), Will, L. (author), Melgert, B.N. (author), van der Zaan, B. (author), van de Steeg, E. (author), Kooter, I.M. (author)Micro- and nanoplastics (MNP) can be found virtually everywhere around us in the biosphere and food chain, therefore humans are continuously exposed to MNP, mainly via inhalation and ingestion. Here, we have applied physiologically relevant human-based advanced in vitro models representing the lung (MucilAir™) and gut (InTESTine™ and Intestinal...article 2022
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Giordano, L. (author), Mihaila, S.M. (author), Eslami Amirabadi, H. (author), Masereeuw, R. (author)Chronic kidney disease (CKD) typically appears alongside other comorbidities, highlighting an underlying complex pathophysiology that is thought to be vastly modulated by the bidirectional gut–kidney crosstalk. By combining advances in tissue engineering, biofabrication, microfluidics, and biosensors, microphysiological systems (MPSs) have...article 2021
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van Berlo, D. (author), van de Steeg, E. (author), Amirabadi, H.E. (author), Masereeuw, R. (author)The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In...article 2021
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Rahman, S. (author), Ghiboud, M. (author), Donkers, J.M. (author), van de Steeg, E. (author), van Tol, E.A.F. (author), Hakvoort, T.B.M. (author), de Jonge, W.J. (author)Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these...article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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Moné, M.J. (author), Pallocca, G. (author), Escher, S.E. (author), Exner, T. (author), Herzler, M. (author), Hougaard Bennekou, S. (author), Kamp, H. (author), Kroese, E.D. (author), Leist, M. (author), Steger-Hartmann, T. (author), van de Water, B. (author)In 2016, the European Commission launched the EU-ToxRisk research project to develop and promote animal-free approaches in toxicology. The 36 partners of this consortium used in vitro and in silico methods in the context of case studies (CSs). These CSs included both compounds with a highly defined target (e.g. mitochondrial respiratory chain...article 2020
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Holmgren, G. (author), Ulfenborg, B. (author), Asplund, A. (author), Toet, K. (author), Andersson, C.X. (author), Hammarstedt, A. (author), Hanemaaijer, J.R.O. (author), Küppers-Munther, B. (author), Synnergren, J. (author)There is a strong anticipated future for human induced pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far, their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The...article 2020
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Verhoeckx, K. (author), lindholm Bøgh, K. (author), Constable, A. (author), Epstein, M.M. (author), hoffmann Sommergruber, K. (author), Holzhauser, T. (author), Houben, G. (author), Kuehn, A. (author), Roggen, E. (author), O'Mahony, L. (author), Remington, B. (author), Crevel, R. (author)The growing world population and increased pressure on agricultural resources are driving a shortage of dietary protein sources. As a result, industry is developing more sustainable novel food protein sources such as insects, algae and duckweed and using new processing techniques. Consumer exposure to these novel or processed proteins, could...article 2020
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Bellmann, S. (author), Krishnan, S. (author), de Graaf, A. (author), de Ligt, R.A. (author), Pasman, W.J. (author), Minekus, M. (author), Havenaar, R. (author)The expected increase of global obesity prevalence makes it necessary to have information about the effects of meal intakes on the feeling of appetite. Because human clinical studies are time and cost intensive, there is a need for a reliable alternative. The aim of this study was to develop and evaluate an in vitro-in silico technology to...article 2019
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Lozano-Ojalvo, D. (author), Benede, S. (author), Antunes, C.M. (author), Bavaro, S.L. (author), Bouchaud, G. (author), Costa, A. (author), Denery-Papini, S. (author), Diaz-Perales, A. (author), Garrido-Arandia, M. (author), Gavrovic-Jankulovic, M. (author), Hayen, S. (author), Martinez-Blanco, M. (author), Molina, E. (author), Monaci, L. (author), Pieters, R.H.H. (author), Villemin, C. (author), Wichers, H.J. (author), Wroblewska, B. (author), Willemsen, L.E.M. (author), Roggen, E.L. (author), van Bilsen, J.H.M. (author)Background: Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the...article 2019
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Verhoeckx, K. (author), Bogh, K.L. (author), Dupont, D. (author), Egger, L. (author), Gadermaier, G. (author), Larre, C. (author), Mackie, A. (author), Menard, O. (author), Adel-Patient, K. (author), Picariello, G. (author), Portmann, R. (author), Smit, J. (author), Turner, P. (author), Untersmayr, E. (author), Epstein, M.M. (author)The current allergenicity assessment of novel proteins is based on the EFSA GMO guidance. Recently, EFSA launched a new guidance document on allergenicity assessment of GM plants (2017). This document describes, amongst other topics, the new scientific and regulatory developments on in vitro protein digestibility tests. The EFSA GMO Panel stated...article 2019
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Horn, G. (author), de Koning, M.C. (author), van Grol, M. (author), Thiermann, H. (author), Worek, F. (author)Poisoning by organophosphorus compounds (OP) is characterized by inhibition of the key enzyme acetylcholinesterase (AChE) and potentially fatal outcomes in humans. Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common...article 2018
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LaCroix, G. (author), Koch, W. (author), Ritter, D. (author), Gutleb, A.C. (author), Larsen, S.T. (author), Loret, T. (author), Zanetti, F. (author), Constant, S. (author), Chortarea, S. (author), Rothen-Rutishauser, B. (author), Hiemstra, P.S. (author), Frejafan, E. (author), Hubert, P. (author), Gribaldo, L. (author), Kearns, P. (author), Aublant, J.M. (author), Diabaté, S. (author), Weiss, C. (author), de Groot, A. (author), Kooter, I.M. (author)In vitro air–liquid interface (ALI) cell culture models can potentially be used to assess inhalation toxicology endpoints and are usually considered, in terms of relevancy, between classic (i.e., submerged) in vitro models and animal-based models. In some situations that need to be clearly defined, ALI methods may represent a complement or an...article 2018
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Reisinger, K. (author), Blatz, V. (author), Brinkmann, J. (author), Downs, T.R. (author), Fischer, A. (author), Henkler, F. (author), Hoffmann, S. (author), Krul, C. (author), Liebsch, M. (author), Luch, A. (author), Pirow, R. (author), Reus, A.A. (author), Schulz, M. (author), Pfuhler, S. (author)Recently revised OECD Testing Guidelines highlight the importance of considering the first site-of-contact when investigating the genotoxic hazard. Thus far, only in vivo approaches are available to address the dermal route of exposure. The 3D Skin Comet and Reconstructed Skin Micronucleus (RSMN) assays intend to close this gap in the in vitro...article 2018
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Remington, B. (author), Broekman, H.C.H. (author), Blom, W.M. (author), Capt, A. (author), Crevel, R.W.R. (author), Dimitrov, I. (author), Faeste, C.K. (author), Fernandez-Canton, R. (author), Giavi, S. (author), Houben, G.F. (author), Glenn, K.C. (author), Madsen, C.B. (author), Kruizinga, A.K. (author), Constable, A. (author)The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or...article 2018