全身干细胞疗法有望治疗严重疾病，但其效率因注射的干细胞穿过血管内皮向患病组织的迁移有限而受到阻碍。了解跨内皮迁移对于改善治疗效果至关重要。我们提出了一种新型 3D 体外血管模型，有助于阐明这些机制，从而促进干细胞疗法的开发。我们的模型通过细胞因子从组织部位扩散到血管中来模拟炎症。它由嵌入纤维蛋白水凝胶中的生物制造血管组成，模仿动脉壁的平滑肌细胞和成纤维细胞组成。可灌注通道内衬有表达血管内皮钙粘蛋白的功能性内皮，提供主动屏障功能，与流动方向一致，并通过原位双光子显微镜重建。 Transwell 测定和 3D 模型均证明了炎症细胞因子的释放（肿瘤坏死因子 α、基质衍生因子 1）。在原理验证实验中，将中成血管细胞（被称为抗肌营养不良症干细胞疗法的有希望的候选者）注射到血管模型中，在毛细血管样流动条件下显示出抗剪切的内皮粘附。我们的 3D 体外模型为研究干细胞跨内皮迁移机制提供了巨大的潜力，有助于开发改进的干细胞疗法。

Systemic stem cell therapies hold promise for treating severe diseases, but their efficiency is hampered by limited migration of injected stem cells across vascular endothelium towards diseased tissues. Understanding transendothelial migration is crucial for improving therapy outcomes. We propose a novel 3D in vitro vessel model that aids to unravel these mechanisms and thereby facilitates stem cell therapy development. Our model simulates inflammation through cytokine diffusion from the tissue site into the vessel. It consists of a biofabricated vessel embedded in a fibrin hydrogel, mimicking arterial wall composition with smooth muscle cells and fibroblasts. The perfusable channel is lined with a functional endothelium which expresses vascular endothelial cadherin, provides an active barrier function, aligns with flow direction and is reconstructed by in situ two-photon-microscopy. Inflammatory cytokine release (tumor necrosis factor α, stromal-derived factor 1) is demonstrated in both a transwell assay and the 3D model. In proof-of-principle experiments, mesoangioblasts, known as a promising candidate for a stem cell therapy against muscular dystrophies, are injected into the vessel model, showing shear-resistant endothelial adhesion under capillary-like flow conditions. Our 3D in vitro model offers significant potential to study transendothelial migration mechanisms of stem cells, facilitating the development of improved stem cell therapies. .© 2024 IOP Publishing Ltd.