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标准化全层人皮肤器官培养模型在自身免疫性水疱病中的转化应用

Translational Use of a Standardized Full Human Skin Organ Culture Model in Autoimmune Blistering Diseases.

作者信息

Burmester Imke A K, Emtenani Shirin, Johns Jan-Gerrit, Ludwig Ralf J, Hammers Christoph M, Hundt Jennifer E

机构信息

Department of Dermatology, University of Lübeck, Lübeck, Germany.

Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.

出版信息

Curr Protoc Pharmacol. 2019 Jun;85(1):e56. doi: 10.1002/cpph.56. Epub 2019 Mar 8.

Abstract

The full human skin organ culture (HSOC) model is a standardized test system for evaluating pharmacological substances on human skin in vitro. The acantholysis associated with pemphigus vulgaris (PV), a severe and potentially life-threatening autoimmune skin blistering disease, can be induced in HSOC by injecting a bi-specific anti-desmoglein (dsg) 1 and 3 single-chain antibody variable fragment (scFv). Compared to cell culture experiments (e.g., induction of dsg3-internalization or keratinocyte dissociation using HaCaT cells or normal human epidermal keratinocytes) the HSOC model is more sophisticated and physiologically relevant. In this model, all three layers of the human skin are present, all cells are sustained in their physiological niche and orientation, and the cell-cell-contacts remain intact. Here we describe a protocol for HSOC, an ex vivo model of human skin, that has proved to be well-established and informative in our laboratory. © 2019 by John Wiley & Sons, Inc.

摘要

完整的人皮肤器官培养(HSOC)模型是一种用于在体外评估药物对人皮肤作用的标准化测试系统。寻常型天疱疮(PV)是一种严重的、可能危及生命的自身免疫性皮肤水疱病,通过注射双特异性抗桥粒芯糖蛋白(dsg)1和3单链抗体可变片段(scFv),可在HSOC中诱导出与PV相关的棘层松解。与细胞培养实验(例如,使用HaCaT细胞或正常人表皮角质形成细胞诱导dsg3内化或角质形成细胞解离)相比,HSOC模型更复杂且在生理上更具相关性。在该模型中,人皮肤的所有三层结构均存在,所有细胞都维持在其生理微环境和方向中,并且细胞间接触保持完整。在此,我们描述了一种HSOC方案,即人皮肤的离体模型,该模型在我们实验室已被证明是成熟且信息丰富的。© 2019 John Wiley & Sons, Inc.

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