Human in vitro hepatic models generate faster drug toxicity data with higher human predictability compared to animal models. However, for long‐term studies, current models require the use of serum and 3D architecture, limiting their utility. Maintaining a functional long‐term human in vitro hepatic culture that avoids complex structures and serum would improve the value of such systems for preclinical studies. This would also enable a more straightforward integration with current multi‐organ devices to study human systemic toxicity to generate an alternative model to chronic animal evaluations. A human primary hepatocyte culture system was characterized for 28 days in 2D and serum‐free defined conditions. Under the studied conditions, human primary hepatocytes maintained their characteristic morphology, hepatic markers and functions for 28 days. The acute and chronic administration of known drugs validated the sensitivity of the system for drug testing. This human 2D model represents a realistic system to evaluate hepatic function for long‐term drug studies, without the need of animal serum, confounding variable in most models, and with less complexity and resultant cost compared to most 3D models. The defined culture conditions can easily be integrated into complex multi‐organ in vitro models for studying systemic effects driven by the liver function for long‐term evaluations.

中文翻译：

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用于药物评价的功能性长期二维无血清人肝体外系统

与动物模型相比，人类体外肝模型产生更快的药物毒性数据，具有更高的人类可预测性。然而，对于长期研究，目前的模型需要使用血清和 3D 结构，限制了它们的实用性。维持功能性的长期人体体外肝培养物，避免复杂的结构和血清，将提高此类系统在临床前研究中的价值。这也将能够更直接地与当前的多器官设备集成，以研究人体系统毒性，从而生成慢性动物评估的替代模型。人类原代肝细胞培养系统在 2D 和无血清限定条件下进行了 28 天的表征。在所研究的条件下，人原代肝细胞在 28 天内保持其特征形态、肝标志物和功能。已知药物的急性和慢性给药验证了该系统对药物测试的敏感性。这种人体 2D 模型代表了一种用于评估长期药物研究的肝功能的现实系统，不需要动物血清，在大多数模型中存在混杂变量，并且与大多数 3D 模型相比，复杂性和成本更低。定义的培养条件可以很容易地整合到复杂的多器官体外模型中，用于研究由肝功能驱动的全身效应，以进行长期评估。与大多数 3D 模型相比，复杂性和成本更低。定义的培养条件可以很容易地整合到复杂的多器官体外模型中，用于研究由肝功能驱动的全身效应，以进行长期评估。与大多数 3D 模型相比，复杂性和成本更低。定义的培养条件可以很容易地整合到复杂的多器官体外模型中，用于研究由肝功能驱动的全身效应，以进行长期评估。