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Three-dimensional cell cultures as a new tool in drug discovery

机译:三维细胞培养作为药物发现的新工具

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摘要

Background and purpose: Producing of reliable information about pharmacological activity of new chemical entities is essential in early stages of drug discovery and development. There is a continuous need for improvement of existing in vitro technologies, in order to get more accurate and more predictive biological data (and for compounds selection) in pre-clinical screening methods and models.Materials and methods: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology.Results: Two-dimensional (2D) cell cultures, in comparison with original tissues, does not fully reproduce in vivo cell growth and differentiation. Therefore, significant efforts have been made toward the development of more realistic three-dimensional (3D) in vitro cell culture models that would better mimic tissue physiology. Basic concepts and advantages of 3D cell cultures, as well as different approaches in technologies that enable the cell growth in 3D will be presented here. Possible applications of 3D cell culture in drug discovery will be discussed, and example of formation of spherical growth of three different human breast cancer cells (MDA-MB-231, SK-BR-3 and T-47D cells) in 3D format will be shown.Conclusions: Although biological significance of obtained data from 2D and 3D cell cultures is still poorly understood, discrepancy of compunds activity illustrated importance of implementation 3D cell culture assays in early part of drug discovery process.
机译:背景和目的:在药物发现和开发的早期阶段,产生有关新化学实体药理活性的可靠信息至关重要。持续需要改进现有的体外技术,以便在临床前筛查方法和模型中获得更准确和更具预测性的生物学数据(以及化合物选择)。材料和方法:二维(2D)细胞与原始组织相比,培养物不能完全复制体内细胞的生长和分化。因此,在开发更逼真的三维(3D)体外细胞培养模型方面做出了巨大的努力,该模型可以更好地模拟组织生理学。结果:与原始组织相比,二维(2D)细胞培养没有充分复制体内细胞的生长和分化。因此,在开发更逼真的三维(3D)体外细胞培养模型方面做出了巨大的努力,该模型将更好地模拟组织生理。这里将介绍3D细胞培养的基本概念和优势,以及使3D细胞生长的技术中的不同方法。将讨论3D细胞培养在药物发现中的可能应用,并将以3D格式形成三种不同的人类乳腺癌细胞(MDA-MB-231,SK-BR-3和T-47D细胞)形成球形生长的例子。结论:尽管从2D和3D细胞培养物中获得的数据的生物学意义仍知之甚少,但化合物活性的差异说明了在药物发现过程的早期实施3D细胞培养测定的重要性。

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