In Vitro Perfused Human Capillary Networks
In Vitro Perfused Human Capillary Networks
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DOI：
10.1089/ten.tec.2012.0430
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发表时间：
2013-09-01
影响因子：
3
通讯作者：
George, Steven C.
中科院分区：
文献类型：
--
作者：
Moya, Monica L.;Hsu, Yu-Hsiang;George, Steven C.
在体外复制复杂的体内组织微环境有可能改变我们的医学方法以及我们对生物学的理解。为了精确地模拟细胞和细胞外基质的3D排列和相互作用，新的微生理系统必须包括血管供应。脉管系统不仅在3D培养中提供氧气、营养物和废物的必要对流运输，而且还耦合和整合器官系统的反应。在这里，我们将联合收割机组织工程和微流体技术相结合，创造了一个体外3D代谢活性基质（类似于1 mm（3）），第一次包含灌注的，活的，动态的，相互连接的人体毛细血管网络。网络内的流速（μ m/s）和剪切速率（s（-1））的范围分别为0-4000和0-1000，因此包括正常生理范围。输注FITC葡聚糖证明微血管（15-50 μ m）在很大程度上不渗透70 kDa。我们的高通量生物导向平台有可能影响与微循环交叉的广泛领域，包括肿瘤转移，药物发现，血管疾病和环境化学毒性。
Replicating in vitro the complex in vivo tissue microenvironment has the potential to transform our approach to medicine and also our understanding of biology. In order to accurately model the 3D arrangement and interaction of cells and extracellular matrix, new microphysiological systems must include a vascular supply. The vasculature not only provides the necessary convective transport of oxygen, nutrients, and waste in 3D culture, but also couples and integrates the responses of organ systems. Here we combine tissue engineering and microfluidic technology to create an in vitro 3D metabolically active stroma (similar to 1 mm(3)) that, for the first time, contains a perfused,living, dynamic, interconnected human capillary network. The range of flow rate (mu m/s) and shear rate (s(-1)) within the network was 0-4000 and 0-1000, respectively, and thus included the normal physiological range. Infusion of FITC dextran demonstrated microvessels (15-50 mu m) to be largely impermeable to 70 kDa. Our high-throughput biology-directed platform has the potential to impact a broad range of fields that intersect with the microcirculation, including tumor metastasis, drug discovery, vascular disease, and environmental chemical toxicity.