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21st Century Cell Culture for 21st Century Toxicology

机译:21世纪毒理学的21世纪细胞培养

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摘要

There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.
机译:在坏模型中没有好的科学。细胞培养特别容易出现伪像。在21世纪,许多新颖的细胞培养技术变得越来越广泛,这些技术可以克服传统文化的局限性,并且在生理上更具相关性。这些措施包括使用干细胞衍生的人类细胞,不同细胞类型的共培养物,支架和细胞外基质,灌注平台(例如微流体),3D培养,片上器官技术,组织结构和器官功能。通过测量生物标志物(例如途径的关键事件),器官特异性功能以及通过高含量方法更全面地评估细胞反应,可以进一步增强此类模型的生理相关性。这些方法仍然很少结合在一起以创建微生理系统。这些技术组合的复杂性可以产生更接近体内情况的结果,但增加了要控制的参数数量,带来了一些新的挑战。实际上,我们并不认为所有细胞培养都必须如此复杂。所做的努力取决于我们的实验和测试的目的。如果只对细胞反应的特定分子靶标感兴趣,那么反映这一点的非常简单的模型可能更适合于实现标准化和高通量。但是,感兴趣的终点和细胞反应的定义越少,我们越应该近似器官或组织样的培养条件,以使生理反应更可能发生。除了这些技术进步以外,细胞培养质量保证和报告以及细胞测试系统验证方面的重要进展还使细胞培养的实用性达到了一个新的水平。良好细胞培养规范(GCCP)的发展和广泛实施是这里的关键。在毒理学中,这是获得有意义和可靠结果的主要前提,最终可以支持风险评估和产品开发决策。

著录项

  • 期刊名称 other
  • 作者

    David Pamies; Thomas Hartung;

  • 作者单位
  • 年(卷),期 -1(30),1
  • 年度 -1
  • 页码 43–52
  • 总页数 24
  • 原文格式 PDF
  • 正文语种
  • 中图分类
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  • 入库时间 2022-08-21 11:11:00

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