Jäger Jonas, Thon Maria, Schimek Katharina, Marx Uwe, Gibbs Susan, Koning Jasper J
Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, 1081HV, The Netherlands.
Amsterdam Institute for Immunology and Infectious Diseases, Inflammatory Diseases, Amsterdam, The Netherlands.
Sci Rep. 2025 Apr 25;15(1):14492. doi: 10.1038/s41598-025-96367-y.
Since the blood and lymphatic endothelium regulates homeostasis and inflammation during health and disease, establishment of vascularized Organ-on-Chip platforms with blood and lymphatic endothelial cells (BEC/LEC) is a pre-requisite to further advance the field of tissue engineering. Here, we aimed to determine whether characteristics of BECs and LECs cultured under flow in a multi-organ-chip (MOC) are influenced by shear stress or inflammation. Dermis-derived primary BECs and LECs were used to endothelialize a MOC followed by culture for up to 14 days at lymphatic and blood flow rates. Under blood flow, both cell types changed morphology, aligned in flow direction, and showed close cell-cell contacts as in in vivo blood vasculature. Under lymphatic flow, neither BEC nor LEC aligned, and both showed a cobblestone-appearance with limited intercellular contacts similar to lymphatics. Cells retained their cell type-specific phenotype and cytokine secretion profiles. CCL21 expression in LECs was rescued by flow, but diminished again with TNFα exposure, together with the LEC-specific markers PROX1 and TFF3. Homeostatic cytokine secretion was higher in BECs, but the response to TNFα was more pronounced in LECs. Results indicate that BEC and LEC phenotype and cytokine secretion is mostly an intrinsic property with only morphology and CCL21 being influenced by flow.
由于血液和淋巴内皮在健康和疾病状态下调节体内平衡和炎症，因此建立具有血液和淋巴内皮细胞（BEC/LEC）的血管化器官芯片平台是进一步推动组织工程领域发展的先决条件。在此，我们旨在确定在多器官芯片（MOC）中流动条件下培养的BEC和LEC的特性是否受剪切应力或炎症的影响。使用源自真皮的原代BEC和LEC对MOC进行内皮化，然后在淋巴和血流速率下培养长达14天。在血流条件下，两种细胞类型均发生形态变化，沿流动方向排列，并显示出与体内血管中类似的紧密细胞间接触。在淋巴流动条件下，BEC和LEC均未排列，且两者均呈现鹅卵石外观，细胞间接触有限，类似于淋巴管。细胞保留了其细胞类型特异性表型和细胞因子分泌谱。流动可恢复LEC中CCL21的表达，但随着TNFα暴露以及LEC特异性标志物PROX1和TFF3的表达，CCL21表达再次降低。BEC中稳态细胞因子分泌较高，但LEC对TNFα的反应更明显。结果表明，BEC和LEC的表型和细胞因子分泌主要是一种内在特性，只有形态和CCL21受流动影响。
