An Accessible Organotypic Microvessel Model Using iPSC-Derived Endothelium.
An Accessible Organotypic Microvessel Model Using iPSC-Derived Endothelium.
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DOI：
10.1002/adhm.201700497
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发表时间：
2018-01
影响因子：
10
通讯作者：
Beebe DJ
中科院分区：
文献类型：
--
作者：
Ingram PN;Hind LE;Jiminez-Torres JA;Huttenlocher A;Beebe DJ
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）来增加相关性，但细胞来源往往被忽视。iPSC衍生的细胞可能比细胞系更具有生理学相关性，同时也比原代细胞变化更小，并且最近的进展已经使它们以类似于细胞系的成本商业化。在这里，我们证明了使用诱导多能干细胞衍生的内皮细胞的功能微血管模型的生成。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，以产生用于体外内皮生物学建模的微血管。iPSC-微血管显示内皮特征，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部署在中性粒细胞的研究中时，iPSC-内皮血管的存在促进中性粒细胞外渗和朝向趋化源的迁移。相关的细胞来源，如iPSC，联合收割机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。
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. iPSCs-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, we demonstrate the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model. 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 towards 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.
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影响因子：
9.3
作者：
Haas, TL;Madri, JA
通讯作者：
Madri, JA
在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
影响因子：
--
作者：
Fukumitsu, Ryu;Takagi, Yasushi;Miyamoto, Susumu
通讯作者：
Miyamoto, Susumu
影响因子：
5.9
作者：
Adams, William J.;Zhang, Yuzhi;Cloutier, Jennifer;Kuchimanchi, Pranati;Newton, Gail;Sehrawat, Seema;Aird, William C.;Mayadas, Tanya N.;Luscinskas, Francis W.;Garcia-Cardena, Guillermo
通讯作者：
Garcia-Cardena, Guillermo
影响因子：
5.4
作者：
Aird, William C.
通讯作者：
Aird, William C.