Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, The Netherlands.
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Lab Chip. 2022 Jan 18;22(2):326-342. doi: 10.1039/d1lc00669j.
The majority of intestinal screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a medium throughput microphysiological system, Intestinal Explant Barrier Chip (IEBC), that creates a dynamic microfluidic microenvironment and prolongs tissue viability. Using a snap fit mechanism, we successfully incorporated human and porcine colon tissue explants and studied tissue functionality, integrity and viability for 24 hours. With a proper distinction of transcellular over paracellular transport (ratio >2), tissue functionality was good at early and late timepoints. Low leakage of FITC-dextran and preserved intracellular lactate dehydrogenase levels indicate maintained tissue integrity and viability, respectively. From a selection of low to high permeability drugs, 6 out of 7 properly ranked according to their fraction absorbed. In conclusion, the IEBC is a novel screening platform benefitting from the complexity of tissue explants and the flow in microfluidic chips.
大多数肠道筛选模型使用的细胞系无法反映人体肠道的复杂性，因此往往无法准确预测肠道药物吸收。组织外植体具有完整的肠道结构和细胞类型多样性，但在静态条件下存活时间短。在这里，我们提出了一种中通量微生理系统，即肠道外植体屏障芯片（IEBC），它创建了一个动态的微流体微环境并延长了组织的存活时间。我们使用快速配合机制成功地将人体和猪结肠组织外植体结合在一起，并研究了组织功能、完整性和 24 小时的活力。通过对跨细胞转运与旁细胞转运（比值>2）进行适当区分，组织功能在早期和晚期都很好。FITC-葡聚糖的低泄漏和保留的细胞内乳酸脱氢酶水平分别表明组织完整性和活力得以维持。从低到高渗透性药物的选择中，根据吸收分数，7 种药物中有 6 种得到了正确排序。总之，IEBC 是一种新型筛选平台，受益于组织外植体的复杂性和微流控芯片中的流动。
