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Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
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肝脂蛋白代谢:在体外细胞基系统中的当前和未来

Izabella Kiss1,2, Nicole Neuwert1, Raimund Oberle1

  • 1Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University Vienna, Vienna 1090, Austria.

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概括
此摘要是机器生成的。

肝脏脂蛋白代谢是代谢疾病的关键. 本综述探讨了实验模型,突出了用于研究脂蛋白疾病和精密医学的先进3D肝脏器官.

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人类 人类 人类 人类 人类 人类 人类iPSCs/ESCs 的使用情况脂蛋白质是一种脂蛋白质.肝脏 肝脏 肝脏 肝脏 肝脏 肝脏代谢 代谢 代谢 代谢有机生物有机物组织培养的组织培养.

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科学领域:

  • 生物化学和分子生物学
  • 肝病学 肝病学是一种肝病学.
  • 代谢疾病 代谢疾病

背景情况:

  • 肝脂蛋白代谢是主要代谢障碍的基础,如家族性高胆固醇血症,代谢综合征和脂肪肝疾病.
  • 脂蛋白吸收和分泌的调节失调驱动这些情况,给健康带来重大挑战.
  • 目前的研究模式面临的局限性包括物种间的差异,伦理限制,以及使用非生理细胞系.

研究的目的:

  • 审查目前脂蛋白代谢的机制概念,重点关注吸收和分泌.
  • 为在脂蛋白研究中使用的实验模型提供全面的概述和批评.
  • 突出先进模型的潜力,特别是3D肝脏有机体,用于未来的研究.

主要方法:

  • 审查现有的关于人类标记物研究,动物模型和二维细胞培养的文献.
  • 分析传统实验系统的局限性和生理相关性.
  • 探索新兴模型,包括精密切割的肝脏切片,芯片上的肝脏以及各种3D肝脏模型 (球体,有机体).

主要成果:

  • 人类和动物脂蛋白代谢之间存在显著差异,影响了模型的可靠性.
  • 2D细胞培养,通常来自癌细胞,缺乏生理相关性.
  • 肝脏的3D模型,特别是从干细胞或肝脏组织中提取的有机体,提供了更好的生理表现.

结论:

  • 先进的3D肝脏模型,特别是有机体,对研究脂蛋白代谢和肝脏疾病有很大的前景.
  • 这些模型可以克服传统系统的局限性,实现更准确的机械洞察力.
  • 未来的研究方向指向将这些先进模型应用于肝脏疾病的精密医学.