Department of Biological and Environmental Engineering, Cornell University, Ithaca, USA.
Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University, Baltimore, USA.
Sci Rep. 2017 Oct 2;7(1):12515. doi: 10.1038/s41598-017-12984-2.
The development of in vitro artificial small intestines that realistically mimic in vivo systems will enable vast improvement of our understanding of the human gut and its impact on human health. Synthetic in vitro models can control specific parameters, including (but not limited to) cell types, fluid flow, nutrient profiles and gaseous exchange. They are also "open" systems, enabling access to chemical and physiological information. In this work, we demonstrate the importance of gut surface topography and fluid flow dynamics which are shown to impact epithelial cell growth, proliferation and intestinal cell function. We have constructed a small intestinal bioreactor using 3-D printing and polymeric scaffolds that mimic the 3-D topography of the intestine and its fluid flow. Our results indicate that TEER measurements, which are typically high in static 2-D Transwell apparatuses, is lower in the presence of liquid sheer and 3-D topography compared to a flat scaffold and static conditions. There was also increased cell proliferation and discovered localized regions of elevated apoptosis, specifically at the tips of the villi, where there is highest sheer. Similarly, glucose was actively transported (as opposed to passive) and at higher rates under flow.
体外人工小肠的发展能够逼真地模拟体内系统，从而极大地提高我们对人类肠道及其对人类健康影响的理解。合成的体外模型可以控制特定的参数，包括（但不限于）细胞类型、流体流动、营养谱和气体交换。它们也是“开放”系统，能够获取化学和生理信息。在这项工作中，我们证明了肠道表面形貌和流体流动动力学的重要性，这些因素会影响上皮细胞的生长、增殖和肠道细胞功能。我们使用 3D 打印和聚合物支架构建了一个小肠生物反应器，该生物反应器模拟了肠道的 3D 形貌及其流体流动。我们的结果表明，与平面支架和静态条件相比，在存在液体剪切和 3D 形貌的情况下，TEER 测量值（通常在静态 2D Transwell 装置中较高）较低。细胞增殖也增加了，并且在绒毛尖端发现了局部区域的凋亡升高，特别是在剪切力最大的地方。同样，葡萄糖在流动条件下以主动运输（而不是被动运输）的方式，并且以更高的速率进行运输。
