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19. Towards More Predictive, Physiological and Animal-free In Vitro Models: Advances in Cell and Tissue Culture 2020 Conference Proceedings

Author

Singh, B, Abdelgawad, ME, Ali, Z, Bailey, J, Budyn, E, Civita, P, Clift, MJD, Connelly, JT, Constant, S, Hittinger, M, Kandarova, H, Kearns, VR, Kiuru, T, Kostrzewski, T, Kress, S, Durban, VM, Lehr, C-M, McMillan, H, Metz, JK, Monteban, V, Movia, D, Neto, C, Owen, C, Paasonen, L, Palmer, KA, Pilkington, GJ, Pilkington, K, Prina-Mello, A, Roper, C, Sheard, J, Smith, S, Turner, JE, Roy, I, Tutty, MA, Velliou, E, Wilkinson, JM, Singh, B, Abdelgawad, ME, Ali, Z, Bailey, J, Budyn, E, Civita, P, Clift, MJD, Connelly, JT, Constant, S, Hittinger, M, Kandarova, H, Kearns, VR, Kiuru, T, Kostrzewski, T, Kress, S, Durban, VM, Lehr, C-M, McMillan, H, Metz, JK, Monteban, V, Movia, D, Neto, C, Owen, C, Paasonen, L, Palmer, KA, Pilkington, GJ, Pilkington, K, Prina-Mello, A, Roper, C, Sheard, J, Smith, S, Turner, JE, Roy, I, Tutty, MA, Velliou, E, and Wilkinson, JM

Abstract

Experimental systems that faithfully replicate human physiology at cellular, tissue and organ level are crucial to the development of efficacious and safe therapies with high success rates and low cost. The development of such systems is challenging and requires skills, expertise and inputs from a diverse range of experts, such as biologists, physicists, engineers, clinicians and regulatory bodies. Kirkstall Limited, a biotechnology company based in York, UK, organised the annual conference, Advances in Cell and Tissue Culture (ACTC), which brought together people having a variety of expertise and interests, to present and discuss the latest developments in the field of cell and tissue culture and in vitro modelling. The conference has also been influential in engaging animal welfare organisations in the promotion of research, collaborative projects and funding opportunities. This report describes the proceedings of the latest ACTC conference, which was held virtually on 30th September and 1st October 2020, and included sessions on in vitro models in the following areas: advanced skin and respiratory models, neurological disease, cancer research, advanced models including 3-D, fluid flow and co-cultures, diabetes and other age-related disorders, and animal-free research. The roundtable session on the second day was very interactive and drew huge interest, with intriguing discussion taking place among all participants on the theme of replacement of animal models of disease.

Published
2021

20. Safer chemicals using less animals: kick-off of the European ONTOX project

Author

Vinken, M., Benfenati, E., Busquet, F., Castell, J., Clevert, D.A., de Kok, T.M., Dirven, H., Fritsche, E., Geris, L., Gozalbes, R., Hartung, T., Jennen, D., Jover, R., Kandarova, H., Kramer, N., Krul, C., Luechtefeld, T., Masereeuw, R., Roggen, E., Schaller, S., Vanhaecke, T., Yang, C., Piersma, A.H., Vinken, M., Benfenati, E., Busquet, F., Castell, J., Clevert, D.A., de Kok, T.M., Dirven, H., Fritsche, E., Geris, L., Gozalbes, R., Hartung, T., Jennen, D., Jover, R., Kandarova, H., Kramer, N., Krul, C., Luechtefeld, T., Masereeuw, R., Roggen, E., Schaller, S., Vanhaecke, T., Yang, C., and Piersma, A.H.

Abstract

The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving increasing attention around the world, and has found its way to legislation, in particular in the European Union. This is aligned by continuing high-level efforts of the European Commission to support development and implementation of 3Rs methods. In this respect, the European project called "ONTOX: ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment" was recently initiated with the goal to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next generation risk assessment. ONTOX will deliver a generic strategy to create new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. For proof-of-concept purposes, focus is put on NAMs addressing adversities in the liver, kidneys and developing brain induced by a variety of chemicals. The NAMs each consist of a computational system based on artificial intelligence and are fed by biological, toxicological, chemical and kinetic data. Data are consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Supported by artificial intelligence, data gaps are identified and are filled by targeted in vitro and in silico testing. ONTOX is anticipated to have a deep and long-lasting impact at many levels, in particular by consolidating Europe's world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.

Published
2021

21. Selected bisphenols and phthalates screened for estrogen and androgen disruption by in silico and in vitro methods

Author

Kandarova, H., Letasiova, S., Bachelor, M., Milasova, T., Markus, J., Ayehunie, S., Dvořáková, M., Kejlová, K., Rucki, M., Jírová, D., Indra, R., Wilhelm, M., Černá, T., Heger, Z., Dostálová, S., Adam, V., Eckschlager, T., Stiborová, M., Hraběta, J., Arlt, V.M., Schmeiser, H.H., Zdurienčíková, M., Gronesová, P., Sedlák, J., Nekvindova, J., Hyrslova Vaculova, A., Soucek, P., Anzenbacher, P., Vondracek, J., Kiss, I., Slaby, O., Kala, Z., Palicka, V., Horváthová, E., Mastihuba, V., Karnišová Potocká, E., Kis, P., Gálová, E., Ševčovičová, A., Klapáková, M., Mastihubová, M., Vondráček, J., Hýžďalová, M., Pivnička, J., Zapletal, O., Neča, J., Machala, M., Figat, R., Wójtowicz, A., Sobczak, M., Śliwińska, A., Pietrosiuk, A., Nałęcz-Jawecki, G., Košťálová, E., Nagyová, V., Kilbergerová, H., Chomová, L., Kurejová, H., Pavlikova, N., Daniel, P., Sramek, J., Jelinek, M., Halada, P., Kovar, J., Jírová, G., Vlková, A., Wittlerová, M., Kašparová, L., Chrz, J., Wittlingerová, Z., Zimová, M., Mráz, J., Hanzlíková, I., Dušková, Š., Tvrdíková, M., Chrástecká, H., Vajtrová, R., Linhart, I., Brandeburová, P., Grenčíková, A., Žabka, D., Mackuľak, T., Ryba, J., Bondarev, D., Kassa, J., Hepnarova, V., Musilek, K., Misik, J., Hatlapatkova, J., Zdarova Karasova, J., Korabecny, J., Gorecki, L., Malinak, D., Hrabinova, M., Soukup, O., Jun, D., Kuca, K., Benkova, M., Marek, J., Sleha, R., Ryskova, L., Matula, M., Tumu, H., Cuffari, B., Billack, B., Koprdová, R., Májeková, M., Kiss, A., Osacká, J., Dremencov, E., Csatlósová, K., Kokras, N., Dalla, C., Švecová, B., Mach, M., Heger, V., Viskupicova, J., Zoofishan, Z., Hunyadi, A., Horakova, L., Bogi, E., Belovicova, K., Csatlosova, K., Moravcíkova, L., Lacinova, L., Dubovicky, M., Sasváriová, M., Kaprinay, B., Salvaras, L., Belovičová, K., Bögi, E., Knézl, V., Barteková, M., Stankovičová, T., Dubovický, M., Hayes, A.W., vom Berg, C., Iskandar, A., Hoeng, J., Peitsch, MC, Dourson, M., Ambrož, M., Lněničková, K., Matoušková, P., Skálová, L., Boušová, I., Andreji, J., Dvořák, P., Anzenbacherová, E., Prokop, J., Mrkvicová, E., Pavlata, L., Zapletalová, I., Šťastník, O., Martinek, P., Kosina, P., Bögi, E, Csatlosová, K., Bernatova, I., Balis, P., Kluknavsky, M., Zemancikova, A., Torok, J., Puzserova, A., Zárybnický, T., Trnčáková, V., Šubrt, Z., Dršata, J., Brucknerová, I., Brucknerova, J., Ujházy, E., Bujňáková Mlynarčíková, A., Scsuková, S., Caloudova, H., Hodkovicova, N., Berlinska, J., Marsalek, B., Panacek, A., Svobodova, Z., Pino, M.A., Capek, J., Brychtová, V., Handl, J., Majtnerová, P., Rousar, T., Dračínská, H., Jelínková, S., Dvořák, J., Dvořáková Líšková, Z., Graňáková, P., Raisová, Stuchlíková L., Podlipná, R., Szotáková, B., Majerová, M., Hamulakova, S., Janovec, L., Čapek, J., Roušar, T., Hanousková, B., Zemanová, K., Hlávková, D., Havelková, B., Beklová, M., Hodek, P., Hucková, P., Hušková, A., Šimůnek, J., Mrázek, J., Hudeček, J., Sehonova, P., Blahova, J., Vaclavik, J., Hrabinová, M., Schmidt, M., Misík, J., Jáklová, K., Pompach, P., Takácsová, P., Vavrová, K., Kopečková, K., Kolárik, M., Jambor, T., Greifova, H., Massanyi, P., Lukac, N., Járová, K., Osičková, P., Kauerová, T., Hamadová, D., Kollár, P., Goněc, T., Kos, J., Jampílek, J., Syrovets, T., Parák, T., Suchý, P., Kobrlova, T., Janockova, J., Kubíčková, B., Rychnová, J., Dostálová, K., Vyhnalová, K., Mrázková, J., Mandys, V., Wimmerová, M., Lazová, J., Bednáriková, M., Imreová, P., Múčková, M., Lipcseyová, D., Benešová, B., Šoltésová Prnová, M., Štefek, M., Viskupičová, J., Láníčková, T., Tománková, V., Cibiček, N., Snášelová, S., Ulrichová, J., Maňáková, E., Hubičková Heringová, L., Skála, M., Skarková, V., Brynychová, V., Souček, P., Heglasová, S., Dugasová, L., Morová, M., Šimončičová, E., Senko, T., Olexová, L., Dzirbíková, Z., Kršková, L., Muckova, L., Jost, P., Pejchal, J., Nowakowska, K., Giebultowicz, J., Kamaszewski, M., Drobniewska, A., Wroczyński, P., Paprskářová, A., Kuzminová, G., Klusáková, J., Hendrych, M., Pavelka, S., Piešová, M., Račková, L., Škandík, M., Straková, Z., Bezek, Š., Jančinová, V., Raisová, L., Martínková, L., Sabolová, D., Imrichová, N., Rendošová, M., Vargová, Z., Lakatoš, B., Gulač, P., Moserová, M., Martínková, E., Frei, E., Syslová, E., Landa, P., Vaněk, T., Harant, K., Šadibolová, M., Deingruberová, K., Špičáková, A., Kraus, P., Strnad, M., Šušaníková, I., Kukurová, Ľ., Forman, V., Mučaji, P., Tvrdý, V., Karlíčková, J., Hanuščinová, L., Mladěnka, P., Ujhazy, E., Koprdova, R., Brucknerova, I., Valachová, K., Topoľská, D., Šoltés, L., Vanduchova, A., Anzenbacherova, E., Vasicek, O., Rubanova, D., Babinkova, P., Fedr, R., Svenda, J., Kubala, L., Vrba, J., Roubalova, L., Vacek, J., Storch, J., Zaltauskaite, J., Jakubynaite, A., Dikšaitytė, A., Januškaitienė, I., Sujetovienė, G., Kacienė, K., Miškelytė, D., and Juknys, R.

Subjects
L-07, L-29, L-06, L-28, L-09, L-08, Article, Abstract Book, L-03, L-25, L-02, L-24, L-05, L-27, L-04, L-26, L-21, L-20, L-01, L-23, L-22, L-18, L-17, L-19, L-30, L-14, L-13, L-16, L-15, L-10, L-32, L-31, L-12, L-11
Published
2018

25. CON4EI: SkinEthicTM human corneal epithelial model

Author

Van Rompay, A.R., primary, Adriaens, E., additional, Alépée, N., additional, Kandarova, H., additional, Drzewiecka, A., additional, Fochtman, P., additional, Gruszka, K., additional, Guest, R., additional, Maglennon, G., additional, Schofield, J., additional, Willoughby, J.A., additional, and Verstraelen, S., additional

Published
2016
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26. CON4EI: Bovine corneal opacity and permeability test method

Author

Verstraelen, S., primary, Adriaens, E., additional, Alépée, N., additional, Kandarova, H., additional, Drzewiecka, A., additional, Fochtman, P., additional, Gruszka, K., additional, Guest, R., additional, Maglennon, G., additional, Schofield, J., additional, Willoughby, J.A., additional, and Van Rompay, A.R., additional

Published
2016
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28. CON4EI: EpiOcular eye irritation test (EIT)

Author

Kandarova, H., primary, Van Rompay, A.R., additional, Adriaens, E., additional, Alépée, N., additional, Drzewiecka, A., additional, Fochtman, P., additional, Gruszka, K., additional, Guest, R., additional, Maglennon, G., additional, Schofield, J., additional, Willoughby, J.A., additional, and Verstraelen, S., additional

Published
2016
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34. LB794 Development, optimization and validation of an in vitro skin irritation test for medical devices using the reconstructed human tissue model EpiDerm

Author

Kandarova, H., primary, Willoughby, J., additional, De Jong, W., additional, Bachelor, M.A., additional, Letasiova, S., additional, Milasova, T., additional, Breyfogle, B., additional, de la Fonteyne, L., additional, Haishima, Y., additional, Ayehunie, S., additional, and Coleman, K., additional

Published
2016
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36. CON4EI: Consortium for in vitro eye irritation testing strategy

Author

Verstraelen, S., primary, Adriaens, E., additional, Alépée, N., additional, Drzewiecka, A., additional, Fochtman, P., additional, Gruszka, K., additional, Guest, R., additional, Kandarova, H., additional, Lenoir, J., additional, Willoughby, J.A.S., additional, and Van Rompay, A., additional

Published
2015
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50. Neurotoxic effect of potential countermeasures in case of nerve agent poisoning

Author

T. Čadež, Z. Kovarik, and Kandarova H., Barroso J

Subjects
cholinesterase, OP poisoning, oximes, antidote
Abstract

Nerve agents (NAs), the deadliest organophosphates, act as inhibitors of cholinesterase enzymes that are vital in cholinergic system. Phosphylation of acetylcholinesterase (AChE), pivotal enzyme in hydrolysis of neurotransmitter acetylcholine, and its related enzyme butyrylcholinesterase (BChE) leads to cholinergic crisis that could ultimately result in death. Medical countermeasures include compounds, containing oxime group with ability for nucleophilic reactivation of phosphylated cholinesterase, that until now have shown limited potency in reactivation of inhibited AChE in central nervous system (CNS). With that purpose, in previous studies we have designed and defined several pyridinium oxime with high potency in reactivation of inhibited BChE that can act as protector of AChE in CNS. Now through a combination of in silico, in vitro, ex vivo results we want to demonstrate a feasible approach to develop safe oxime-assisted bioscavenger of NAs based on the efficient reactivation of BChE. Selected oximes have shown to be most prominent reactivators of BChE inhibited with nerve agent cyclosarin through their overall kinetic reactivation rate. Tested oximes also shown no effect on viability of neuroblastoma cell upon 4- hours treatment, contrary to cyclosarin exposure. Furthermore, the cytotoxicity profiles on neural cells were determent for oxime-assisted catalytic BChE degradation of cyclosarin, where in case of post-treatment approach 50 % of neural cells had preserved, while in pre-treatment almost all of the cells have been protected. The most promising bioscavenger combination was then evaluated in ex vivo conditions of human blood resulting in up to 80% of restored phosphylated cholinesterase activity within a short time. Taken all together our findings

Published
2022

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