Gordon Sarah, Daneshian Mardas, Bouwstra Joke, Caloni Francesca, Constant Samuel, Davies Donna E, Dandekar Gudrun, Guzman Carlos A, Fabian Eric, Haltner Eleonore, Hartung Thomas, Hasiwa Nina, Hayden Patrick, Kandarova Helena, Khare Sangeeta, Krug Harald F, Kneuer Carsten, Leist Marcel, Lian Guoping, Marx Uwe, Metzger Marco, Ott Katharina, Prieto Pilar, Roberts Michael S, Roggen Erwin L, Tralau Tewes, van den Braak Claudia, Walles Heike, Lehr Claus-Michael
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI) and Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
ALTEX. 2015;32(4):327-78. doi: 10.14573/altex.1510051.
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.
人体外部上皮组织模型——即皮肤、肠道和肺——已在研究和工业环境中得到有效应用,成为动物实验颇具吸引力的替代方法。目前,这些领域采用了多种方法来构建这些屏障模型,从利用离体组织到构建体外重建模型,再到基于芯片的技术、合成膜系统,以及当前越来越受关注的计算机模拟方法。来自学术界、工业界和监管机构的上皮屏障领域国际专家小组齐聚一堂,介绍皮肤、肠道和肺部屏障非动物模型在其各个应用领域的当前技术水平,并讨论基于研究、由行业驱动以及与监管相关的未来方向,包括新模型的开发和现有测试方法的改进。模型的相关性和偏好、验证和标准化、接受度以及简单性与复杂性的需求等问题是讨论的焦点主题。与会专家在本报告中介绍了研讨会报告和讨论的结果,涉及上皮屏障模型利用和开发的现状及未来方向。