<br>泡沫细胞形成的生物工程血管模型,ACS Biomaterials Science & Engineering

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泡沫细胞形成的生物工程血管模型
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-11-29 , DOI: 10.1021/acsbiomaterials.3c01308
Ying Zhou _{1,

2} , Nadia Chandra Sekar ₂ , Peter Thurgood _{1,

3} , Scott Needham ₄ , Karlheinz Peter _{1,

5} , Khashayar Khoshmanesh _{1,

3} , Sara Baratchi _{1,

2,

5}

Affiliation

泡沫细胞形成是一种复杂的血管病理学，其特征是一系列事件，包括内皮功能障碍、炎症和血管壁下方免疫细胞的积累。需要能够重现这些事件的新型生物工程模型，以更好地了解泡沫细胞形成发展背后的复杂病理过程，从而需要先进的生物工程平台来筛选药物。在这里，我们生成了一个微流体血管模型，其中包含涂有内皮层的三维（3D）细胞外基质。该系统使我们能够在动态微环境下进行实验，重现天然血管区域的复杂性。使用该模型，我们研究了调节单核细胞粘附和迁移以及血管壁内泡沫细胞形成的效应器。我们发现单核细胞粘附和迁移受到内皮和单核细胞本身的调节。仅当内皮细胞在血管模型中培养时，单核细胞才会迁移到细胞外基质中。此外，内皮层暴露于肿瘤坏死因子α（TNF-α）和低剪切应力都会增加单核细胞向内皮下空间向基质的迁移。此外，我们还展示了外周血单核细胞 (PBMC) 转入血管壁 3 天后泡沫细胞形成的过程。我们发现，将 PBMC 预先暴露于高剪切率会增加它们通过 TNF-α 处理的内皮细胞的粘附和迁移，但不会影响它们形成泡沫细胞的能力。我们模型的多功能性允许在定制的病理条件下对泡沫细胞形成进行机械研究。

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Bioengineered Vascular Model of Foam Cell Formation

Foam cell formation is a complex blood vessel pathology, which is characterized by a series of events, including endothelium dysfunction, inflammation, and accumulation of immune cells underneath the blood vessel walls. Novel bioengineered models capable of recapitulating these events are required to better understand the complex pathological processes underlying the development of foam cell formation and, consequently, advanced bioengineered platforms for screening drugs. Here, we generated a microfluidic blood vessel model, incorporating a three-dimensional (3D) extracellular matrix coated with an endothelial layer. This system enables us to perform experiments under a dynamic microenvironment that recapitulates the complexities of the native vascular regions. Using this model, we studied the effectors that regulate monocyte adhesion and migration, as well as foam cell formation inside vessel walls. We found that monocyte adhesion and migration are regulated by both the endothelium and monocytes themselves. Monocytes migrated into the extracellular matrix only when endothelial cells were cultured in the vessel model. In addition, the exposure of an endothelial layer to tumor necrosis factor α (TNF-α) and low shear stress both increased monocyte migration into the subendothelial space toward the matrix. Furthermore, we demonstrated the process of foam cell formation, 3 days after transmigration of peripheral blood mononuclear cells (PBMCs) into the vessel wall. We showed that pre-exposure of PBMCs to high shear rates increases their adhesion and migration through the TNF-α-treated endothelium but does not affect their capacity to form foam cells. The versatility of our model allows for mechanistic studies on foam cell formation under customized pathological conditions.

更新日期：2023-11-29

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