Cook Sophie R, Ball Alexander G, Mohammad Anwaruddin, Pompano Rebecca R
Department of Chemistry, University of Virginia, Charlottesville, VA, USA.
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
Lab Chip. 2025 Jan 14;25(2):155-174. doi: 10.1039/d4lc00489b.
Multi-organ-on-chip systems (MOOCs) have the potential to mimic communication between organ systems and reveal mechanisms of health and disease. However, many existing MOOCs are challenging for non-experts to implement due to complex tubing, electronics, or pump mechanisms. In addition, few MOOCs have incorporated immune organs such as the lymph node (LN), limiting their applicability to model critical events such as vaccination. Here we developed a 3D-printed, user-friendly device and companion tubing-free impeller pump with the capacity to co-culture two or more tissue samples, including a LN, under a recirculating common media. Native tissue structure and immune function were incorporated by maintaining slices of murine LN tissue in 3D-printed mesh supports for at least 24 h. In a two-compartment model of a LN and an upstream injection site in mock tissue, vaccination of the multi-compartment chip was similar to vaccination in terms of locations of antigen accumulation and acute changes in activation markers and gene expression in the LN. We anticipate that in the future, this flexible platform will enable models of multi-organ immune responses throughout the body.
多器官芯片系统(MOOCs)有潜力模拟器官系统之间的通讯,并揭示健康与疾病的机制。然而,由于复杂的管道、电子设备或泵机制,许多现有的MOOCs对于非专业人员来说实施起来具有挑战性。此外,很少有MOOCs纳入了免疫器官,如淋巴结(LN),这限制了它们在模拟诸如疫苗接种等关键事件方面的适用性。在此,我们开发了一种3D打印的、用户友好型设备以及配套的无管道叶轮泵,其能够在循环的共同培养基下共培养两个或更多组织样本,包括一个LN。通过将小鼠LN组织切片在3D打印的网状支架中维持至少24小时,整合了天然组织结构和免疫功能。在模拟组织中LN和上游注射部位的双隔室模型中,多隔室芯片的疫苗接种在抗原积累位置以及LN中激活标志物和基因表达的急性变化方面与实际疫苗接种相似。我们预计,在未来,这个灵活的平台将能够构建全身多器官免疫反应的模型。