An Accessible Organotypic Microvessel Model Using iPSC‐Derived Endothelium,Advanced Healthcare Materials

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An Accessible Organotypic Microvessel Model Using iPSC‐Derived Endothelium
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-08-07 , DOI: 10.1002/adhm.201700497
Patrick N. Ingram ₁ , Laurel E. Hind ₂ , Jose A. Jiminez-Torres ₁ , Anna Huttenlocher ₂ , David J. Beebe _{1,

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Affiliation

While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)‐derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell‐derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient‐specific models.

中文翻译：

使用iPSC衍生的内皮细胞可访问的器官型微血管模型

尽管有机型方法有望通过增加复杂性（例如3D细胞外微环境，结构/功能关系，多种细胞类型的存在）来增加相关性，但通常会忽略细胞来源。诱导多能干细胞（iPSC）衍生的细胞可能比细胞系更具生理相关性，同时也比原代细胞具有更少的可变性，并且最近的进展已使其以与细胞系相似的成本商业化销售。在此，证明了诱导多能干细胞衍生内皮细胞在功能性微血管模型生成中的应用。该设计方法提供的高精度结构和微环境控制与iPSC的优势协同作用，可生产用于体外模拟内皮生物学的微血管。iPSC微血管显示出内皮特征，表现出屏障功能，分泌血管生成和炎性介质，并通过改变血管表型来响应细胞外微环境的变化。重要的是，当在先天免疫募集期间用于中性粒细胞的研究时，iPSC内皮血管的存在促进了中性粒细胞的外渗和向趋化性源的迁移。相关的细胞来源（例如iPSC）与器官型模型相结合，为改善和日益普及的体外组织，疾病和患者特异性模型开辟了道路。当在先天免疫募集期间用于中性粒细胞的研究时，iPSC内皮血管的存在促进了中性粒细胞的外渗和向趋化性源的迁移。相关的细胞来源（例如iPSC）与器官型模型相结合，为改善和日益普及的体外组织，疾病和患者特异性模型开辟了道路。当在先天免疫募集期间用于中性粒细胞的研究时，iPSC内皮血管的存在促进了中性粒细胞的外渗和向趋化性源的迁移。相关的细胞来源（例如iPSC）与器官型模型相结合，为改善和日益普及的体外组织，疾病和患者特异性模型开辟了道路。

更新日期：2017-08-07

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