Non-Animal Models of Epithelial Barriers (Skin, Intestine and Lung) in Research, Industrial Applications and Regulatory Toxicology

被引:105
作者
Gordon, Sarah [1 ,2 ]
Daneshian, Mardas [3 ]
Bouwstra, Joke [4 ]
Caloni, Francesca [5 ]
Constant, Samuel [6 ]
Davies, Donna E. [7 ,8 ]
Dandekar, Gudrun [9 ,10 ]
Guzman, Carlos A. [11 ]
Fabian, Eric [12 ]
Haltner, Eleonore [13 ]
Hartung, Thomas [3 ,14 ]
Hasiwa, Nina [3 ]
Hayden, Patrick [15 ]
Kandarova, Helena [16 ]
Khare, Sangeeta [17 ]
Krug, Harald F. [18 ]
Kneuer, Carsten [19 ]
Leist, Marcel [3 ]
Lian, Guoping [20 ,21 ]
Marx, Uwe [22 ,23 ]
Metzger, Marco [9 ,10 ]
Ott, Katharina [12 ]
Prieto, Pilar [24 ]
Roberts, Michael S. [25 ,26 ]
Roggen, Erwin L. [27 ]
Tralau, Tewes [28 ]
van den Braak, Claudia [29 ]
Walles, Heike [9 ,10 ]
Lehr, Claus-Michael [1 ,2 ]
机构
[1] Univ Saarland, Helmholtz Ctr Infect Res HZI, Helmholtz Inst Pharmaceut Res Saarland HIPS, Dept Drug Delivery DDEL, D-66123 Saarbrucken, Germany
[2] Univ Saarland, Dept Pharm, D-66123 Saarbrucken, Germany
[3] Univ Konstanz, Ctr Alternat Anim Testing Europe, Constance, Germany
[4] Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Delivery Technol, Leiden, Netherlands
[5] Univ Milan, Dept Hlth Anim Sci & Food Safety VESPA, Milan, Italy
[6] Epithelix Sarl, Geneva, Switzerland
[7] Univ Southampton, Fac Med, Clin & Expt Sci, Southampton SO9 5NH, Hants, England
[8] Southampton Univ Hosp, NIHR Resp Biomed Res Unit, Southampton, Hants, England
[9] Univ Hosp Wurzburg, Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Translat Ctr Regenerat Therapies Oncol & Musculos, Wurzburg Branch, Wurzburg, Germany
[10] Univ Hosp Wurzburg, Dept Tissue Engn & Regenerat Med, Wurzburg, Germany
[11] Helmholtz Ctr Infect Res HZI, Dept Vaccinol & Appl Microbiol, Braunschweig, Germany
[12] BASF SE, Expt Toxicol & Ecol, Ludwigshafen, Germany
[13] Across Barriers GmbH, Saarbrucken, Germany
[14] Johns Hopkins Univ, Ctr Alternat Anim Testing, Bloomberg Sch Publ Hlth, Baltimore, MD USA
[15] MatTek Corp, Ashland, MA USA
[16] MatTek In Vitro Life Sci Labs, Bratislava, Slovakia
[17] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA
[18] Empa Swiss Fed Inst Mat Sci Technol, St Gallen, Switzerland
[19] German Fed Inst Risk Assessment BfR, Dept Pesticide Safety, Berlin, Germany
[20] Unilever Res Colworth, Sharnbrook, Beds, England
[21] Univ Surrey, Dept Chem & Proc Engn, Guildford GU2 5XH, Surrey, England
[22] Tech Univ Berlin, Berlin, Germany
[23] TissUse Inc, Spreenhagen, Berlin, Germany
[24] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, EURL ECVAM,Syst Toxicol Unit, I-21020 Ispra, Italy
[25] Univ Queensland, Sch Med, Therapeut Res Ctr, Brisbane, Qld, Australia
[26] Univ S Australia, Adelaide, SA 5001, Australia
[27] 3Rs Management & Consulting ApS, Lyngby, Denmark
[28] German Fed Inst Risk Assessment BfR, Dept Chem & Prod Safety, Berlin, Germany
[29] Danone Corp, Nutricia Res, Utrecht, Netherlands
基金
英国医学研究理事会; 英国国家替代、减少和改良动物研究中心; 英国生物技术与生命科学研究理事会;
关键词
in vitro models; epithelial cell culture; permeability; transport studies; cytotoxicity; IN-VITRO MODEL; ON-A-CHIP; RECONSTRUCTED HUMAN EPIDERMIS; RESPIRATORY SYNCYTIAL VIRUS; ASTHMATIC BRONCHIAL EPITHELIUM; MEMBRANE-PERMEABILITY ASSAY; PULMONARY DRUG-DELIVERY; VESICLE-BASED BARRIER; ORGAN-CULTURE METHOD; WATER-SOLUBLE DRUGS;
D O I
10.14573/altex.1510051
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Models of the outer epithelia of the human body namely the skin, the intestine and the lung have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.
引用
收藏
页码:327 / 378
页数:52
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