Keuper-Navis Marit, Eslami Amirabadi Hossein, Donkers Joanne, Walles Markus, Poller Birk, Heming Bo, Pieters Lisanne, de Wagenaar Bjorn, Myszczyszyn Adam, Sinnige Theo, Spee Bart, Masereeuw Rosalinde, van de Steeg Evita
Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands.
AZAR Innovations, 3584 CH Utrecht, The Netherlands.
Micromachines (Basel). 2024 Nov 30;15(12):1464. doi: 10.3390/mi15121464.
To accurately measure permeability of compounds in the intestine, there is a need for preclinical in vitro models that accurately represent the specificity, integrity and complexity of the human small intestinal barrier. Intestine-on-chip systems hold considerable promise as testing platforms, but several characteristics still require optimization and further development.
An established intestine-on-chip model for tissue explants was adopted for intestinal cell monolayer culture. A 3D-printed culture disc was designed to allow cell culture in static conditions and subsequent permeability studies in a dynamic environment. Membrane characteristics and standardized read-outs were investigated and compared to traditional permeability studies under static conditions.
By starting cultures outside the chip in conventional wells plates, the new cell disc design could support accurate cell monolayer formation for both Caco-2 and human enteroids. When transferred to the chip with laminar flow, there was accurate detection of barrier integrity (FD4 and Cascade Blue) and permeability (atenolol/antipyrine). Both flow and membrane characteristics had a significant impact on permeability outcomes.
This novel intestinal cell-on-chip system offers large flexibility for intestinal permeability studies, although it still requires validation with more compounds to reveal its full potential.
为了准确测量化合物在肠道中的渗透性，需要能够准确体现人类小肠屏障特异性、完整性和复杂性的临床前体外模型。芯片上肠道系统作为测试平台具有很大潜力，但仍有几个特性需要优化和进一步开发。
采用一种已建立的用于组织外植体的芯片上肠道模型进行肠道细胞单层培养。设计了一个3D打印的培养盘，以便在静态条件下进行细胞培养，并在动态环境中进行后续的渗透性研究。研究了膜的特性和标准化读数，并与静态条件下的传统渗透性研究进行了比较。
通过在传统孔板中于芯片外开始培养，新的细胞盘设计能够支持Caco-2细胞和人肠类器官形成准确的细胞单层。当转移到具有层流的芯片中时，能够准确检测屏障完整性（FD4和级联蓝）和渗透性（阿替洛尔/安替比林）。流动和膜的特性对渗透性结果都有显著影响。
这种新型的芯片上肠道细胞系统为肠道渗透性研究提供了很大的灵活性，尽管仍需要用更多化合物进行验证以揭示其全部潜力。
