Organotypic liver culture models: meeting current challenges in toxicity testing.
Organotypic liver culture models: meeting current challenges in toxicity testing.
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器官肝培养模型：应对毒性测试中当前的挑战。
DOI：
10.3109/10408444.2012.682115
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发表时间：
2012-07
影响因子：
5.9
通讯作者：
Powers MJ
中科院分区：
文献类型：
--
作者：
LeCluyse EL;Witek RP;Andersen ME;Powers MJ
从体外数据预测化学品诱导的人类肝毒性仍然是制药和化学工业的一个重大挑战。通常，常规的体外肝模型系统（即原代或永生化肝细胞的2-D静态单培养物）受限于它们不能在培养物中随时间保持组织型和表型特征，包括清除和生物活化途径的稳定表达，以及对化学暴露的复杂适应性反应。这些系统对于长期毒性评价和阐明化学暴露的初级和次级适应中涉及的关键细胞和分子事件，或用于识别炎症、增殖和凋亡的重要介质，都不太理想。在实施更有效的体外-体内外推和人体风险评估策略方面取得的进展取决于组织培养技术的重大进步和生物复杂性的提高。本文介绍了目前和正在进行的需要更相关的，器官型的体外替代系统的人肝和最近的努力，重建多细胞结构和血液动力学特性的肝脏使用新的文化平台。随着这些系统越来越广泛地用于化学和药物毒性测试，将有相应的需要建立标准化的测试条件，终点分析和验收标准。未来，样本通量和生物相关性之间的平衡方法应提供更好的体外工具，与动物试验互补，并有助于进行更具预测性的人类风险评估。
Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment.
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影响因子：
13.5
作者：
ARTERBURN, LM;ZURLO, J;HEIFETZ, AH
通讯作者：
HEIFETZ, AH
影响因子：
3.2
作者：
Binda, D;Lasserre-Bigot, D;Richert, L
通讯作者：
Richert, L
DOI：
10.1083/jcb.201009141
发表时间：
2011-03-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baum B;Georgiou M
通讯作者：
Georgiou M
影响因子：
15.9
作者：
BISSELL, DM;ARENSON, DM;ROLL, FJ
通讯作者：
ROLL, FJ
影响因子：
1.9
作者：
BISSELL, DM;CHOUN, MO
通讯作者：
CHOUN, MO