Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, WIMR I Room 6028, 1111 Highland Ave, Madison, WI, 53705, USA.
Departments of Pediatrics and Medical Microbiology and Immunology, University of Wisconsin-Madison, Microbial Sciences Building Room 4205, 1550 Linden Dr, Madison, WI, 53705, USA.
Adv Healthc Mater. 2018 Jan;7(2). doi: 10.1002/adhm.201700497. Epub 2017 Aug 7.
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.
虽然器官型方法通过增加复杂性（例如 3D 细胞外微环境、结构/功能关系、多种细胞类型的存在）来提高相关性，但细胞来源往往被忽视。诱导多能干细胞（iPSC）衍生的细胞比细胞系更具有生理相关性，同时也比原代细胞更具可变性，最近的进展使它们在成本上类似于细胞系，并且可以商业化获得。在这里，展示了诱导多能干细胞衍生的内皮细胞用于生成功能性微血管模型的用途。设计方法提供的高精度结构和微环境控制与 iPSC 的优势相结合，可用于体外模拟内皮生物学的微血管。iPSC 微血管表现出内皮特征，表现出屏障功能，分泌血管生成和炎症介质，并通过改变血管表型对细胞外微环境的变化做出反应。重要的是，当在先天免疫募集过程中研究中性粒细胞时，iPSC 内皮血管的存在促进了中性粒细胞的渗出和向趋化源的迁移。相关的细胞来源，如 iPSC，与器官型模型相结合，为改进和越来越容易获得的体外组织、疾病和患者特异性模型开辟了道路。
