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Human Liver Slices to Investigate Injury and Repair

机译:人类的肝脏切片调查伤害和修复

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Introduction: Liver organ slices are a multicellular three-dimensional tissue model, relevant for defining the dose–response profile of drug-induced injury, and for demonstrating which is the more sensitive species to the injury. In this organotypic ex vivo model, tissue architecture is maintained, including the cell–cell and cell–matrix interactions to mimic in vivo function. Materials and Methods: Extending the tissue viability for up to 7 days in culture expands the use of this model for studying pathways of injury and repair after the multiple dosing of a drug. Gene expression profiles plus functional measurements and histopathology provide mechanistic information of drug action on key pathways that are causal to organ dysfunction and injury. Discussion: Liver toxicity, detected in the animal in vivo studies, can be reproduced in the liver slice model with animal tissue, and then compared with human liver slice drug response. Conclusions: This allows to define the relevance of the toxicity for humans and to define the drug concentration range that will induce the potential side effects in humans compared with that in animals, as well as to identify potential biomarkers of the side effect.
机译:作品简介:肝脏器官切片是一个多细胞的三维组织模型,相关定义剂量反应概要文件药物引起的损伤,和展示哪个是更敏感的物种受伤。架构是维护,包括信息和cell-matrix交互模拟体内的功能。扩展组织生存7天在文化扩展这个模型的使用学习途径后的损伤和修复多次给药的药物。概要文件+功能测量和组织病理学提供机械的信息药物作用的主要途径是因果器官功能障碍和损伤。毒性,发现在动物体内研究,也可以复制在肝脏切片模型动物组织,然后与人类肝脏片药物反应。定义人类的毒性的相关性和定义的药物浓度范围将诱导人类潜在的副作用与动物相比,以及识别潜在的生物标记物的副作用。

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