开发一个高度差异化的人类初级近接管道MPS模型 (a近似MPS流)
Francesca Pisapia1, Donovan O'Brien1, Elena Tasinato1,2
1Newcells Biotech Ltd., The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK.
Bioengineering (Basel, Switzerland)
|January 26, 2024
概括
在流体流动下使用人类近道管细胞开发新的微生理系统 (MPS) 模型,大大提高了它们的功能和药物运输能力,提高了对人类结果的预测准确性.
科学领域:
- 生物医学工程 生物医学工程
- 脏生理学 脏生理学
- 药物开发 药物开发
背景情况:
- 脏近道管 (PT) 对于药物排泄至关重要,也是药物毒性的常见部位.
- 现有的动物模型很难预测人类对药物的反应.
- 需要精确的PT功能模型来评估药物的疗效和毒性.
研究的目的:
- 开发一个生理上相关的微生理系统 (MPS) 模型的人类PT.
- 评估流体介质流动和剪切应力对人类PT细胞 (hPTC) 的影响.
- 评估新型MPS模型的改进功能和预测潜力.
主要方法:
- 初级人类PT细胞 (hPTC) 在流体介质流 (0.01-0.2Pa剪切应力) 下在aProximate MPS Flow平台上培养.
- 分析了细胞极性,输送体表达 (OAT1,OAT3,OCT2,MATE1,URAT1,GLUT9,MDR1,MRP2,巨,库比林) 和乳毛蛋白表达.
- 使用免疫光显微镜来确认蛋白质的定位和表达.
- 测量了对西斯普拉丁的敏感性和肌素和FITC-专素的吸收.
主要成果:
- 与静态培养物相比,MPS模型中的hPTCs表现出恢复的极性和显著更高的关键药物载体表达.
- 证实了OAT1,OAT3和乳毛蛋白的表达增加.
- 该模型显示,在流体剪切应力下,对西斯普拉丁的敏感性增加,肌素和FITC-专素的吸收增加.
结论:
- 在aProximate MPS Flow平台上的流体介质流下生长hPTC显著提高了它们的表型和功能.
- 这种新的MPS模型为研究PT药物相互作用提供了更好的实用性和近乎生理相关性.
- 该模型为评估药物疗效和预测体内人类结果提供了一个更准确的平台.
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