Engineering of functional, perfusable 3D microvascular networks on a chip
Engineering of functional, perfusable 3D microvascular networks on a chip
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DOI：
10.1039/c3lc41320a
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发表时间：
2013-01-01
期刊：
影响因子：
6.1
通讯作者：
Jeon, Noo Li
中科院分区：
文献类型：
--
作者：
Kim, Sudong;Lee, Hyunjae;Jeon, Noo Li
在体外生成可灌流的3D微血管是组织工程学的一个重要目标，也是血管功能可靠建模的一个重要目标。到目前为止，体外血管模型还不能准确地再现内皮细胞的动力学和反应，以形成可灌流的和有功能的3D血管网络。在这里，我们描述了一个基于微流体的平台，通过该平台，我们对正常发育和血管生成过程中发现的自然细胞程序进行建模，以形成完整的3D微血管和肿瘤血管的可灌流网络，该网络基于内皮细胞与基质成纤维细胞、周细胞或癌细胞的空间控制共培养。微血管具有体内血管特有的形态和生化标志，具有较强的屏障功能和长期稳定性。开放、通畅的微血管系统允许营养物质、化合物、生物分子和细胞悬浮液以及流动诱导的机械刺激进入内皮的管腔空间，并表现出对生理切应力的忠实反应，如细胞骨架重排和一氧化氮合成增加所证明的那样。这个简单而通用的平台在血管生理学研究以及开发用于药物筛选的血管化芯片上器官和人类疾病模型方面提供了广泛的应用。
Generating perfusable 3D microvessels in vitro is an important goal for tissue engineering, as well as for reliable modelling of blood vessel function. To date, in vitro blood vessel models have not been able to accurately reproduce the dynamics and responses of endothelial cells to grow perfusable and functional 3D vascular networks. Here we describe a microfluidic-based platform whereby we model natural cellular programs found during normal development and angiogenesis to form perfusable networks of intact 3D microvessels as well as tumor vasculatures based on the spatially controlled co-culture of endothelial cells with stromal fibroblasts, pericytes or cancer cells. The microvessels possess the characteristic morphological and biochemical markers of in vivo blood vessels, and exhibit strong barrier function and long-term stability. An open, unobstructed microvasculature allows the delivery of nutrients, chemical compounds, biomolecules and cell suspensions, as well as flow-induced mechanical stimuli into the luminal space of the endothelium, and exhibits faithful responses to physiological shear stress as demonstrated by cytoskeleton rearrangement and increased nitric oxide synthesis. This simple and versatile platform provides a wide range of applications in vascular physiology studies as well as in developing vascularized organ-on-a-chip and human disease models for pharmaceutical screening.