一个无,高通量微生理系统模拟十二指肠表皮的肠内和对屏障功能的影响
Kyla N Kaiser1, Jessica R Snyder2, Ryan A Koppes1,2
1Department of Chemical Engineering, Northeastern University, Boston, MA 02155, USA.
概括
这项研究引入了带有肠道神经元和上皮的3D器官芯片模型,增强了肠道屏障功能,并为胃肠道研究提供了更准确的体外模型.
科学领域:
- 生物医学工程
- 胃肠病学
- 神经科学
背景情况:
- 肠道神经元调节小肠道平衡,但它们在大多数体外模型中缺乏,这限制了研究.
- 肠道神经元的失调与胃肠道和神经退行性疾病有关.
研究的目的:
- 开发一个高吞吐量3D微生理系统 (MPS),其中包括初级肠神经元和上皮.
- 为研究肠道创建一个更加仿生和生理相关的体外模型.
主要方法:
- 设计了12个单元的3D MPS设备,支持与封装的初级肠神经元接口的初级上皮单层.
- 使用引力驱动的流动和实验室摇摆器来诱导生物模拟切割应力和营养物质的输送.
- 进行过脑膜电阻 (TEER) 和透性测试以评估屏障完整性.
主要成果:
- 与肠道神经系统 (ENS) 共同培养系统的存在显著提高了屏障完整性 (1.25倍的抗性,10%的透性).
- 导致表皮生长因子 (EGF) 显著降低1. 4倍.
- 刺激改变了上皮细胞中的细胞因子表达和WNT通路,表明了更多的仿生反应.
结论:
- 开发的3D MPS与肠内化为胃肠道研究提供了更具生理相关性的体外模型.
- 在肠道模型中建立生物模拟屏障功能和细胞反应至关重要.
- 这种模式促进了胃肠道疾病和神经退行性疾病的研究.
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