Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Lab Chip. 2018 Oct 9;18(20):3079-3085. doi: 10.1039/c8lc00910d.
Current in vitro approaches and animal models have critical limitations for modeling human gastrointestinal diseases because they may not properly represent multicellular human primary tissues. Therefore, there is a need for model platforms that recapitulate human in vivo development, physiology, and disease processes to validate new therapeutics. One of the major steps toward this goal was the generation of three-dimensional (3D) human gastric organoids (hGOs) via the directed differentiation of human pluripotent stem cells (hPSCs). The normal functions and diseases of the stomach occur in the luminal epithelium, however accessing the epithelium on the inside of organoids is challenging. We sought to develop a bioengineered platform to introduce luminal flow through hGOs to better model in vivo gastric functions. Here, we report an innovative microfluidic imaging platform housing hGOs with peristaltic luminal flow in vitro. This human stomach-on-a-chip allows robust, long-term, 3D growth of hGOs with the capacity for luminal delivery via a peristaltic pump. Organoids were cannulated and medium containing fluorescent dextran was delivered through the lumen using a peristaltic pump. This system also allowed us to rhythmically introduce stretch and contraction to the organoid, reminiscent of gastric motility. Our platform has the potential for long-term delivery of nutrients or pharmacological agents into the gastric lumen in vitro for the study of human gastric physiology, disease modeling, and drug screening, among other possibilities.
目前，用于模拟人类胃肠道疾病的体外方法和动物模型存在着严重的局限性，因为它们可能无法正确代表多细胞的人类原发性组织。因此，需要能够重现人类体内发育、生理和疾病过程的模型平台，以验证新的治疗方法。实现这一目标的重要步骤之一是通过定向分化人类多能干细胞（hPSC）来生成三维（3D）人类胃类器官（hGO）。胃的正常功能和疾病发生在腔上皮中，然而，获取类器官内部的上皮组织是具有挑战性的。我们试图开发一种生物工程平台，通过 hGO 引入腔内流动，以更好地模拟体内胃功能。在这里，我们报告了一种创新的微流控成像平台，该平台在体外为 hGO 提供蠕动腔内流动。这种“人胃芯片”允许 hGO 进行稳健的、长期的 3D 生长，并且能够通过蠕动泵进行腔内输送。通过使用蠕动泵将含有荧光葡聚糖的培养基输送到腔中，对类器官进行了插管。该系统还使我们能够有节奏地对类器官进行拉伸和收缩，类似于胃动力。我们的平台具有在体外向胃腔长期输送营养物质或药物的潜力，可用于研究人类胃生理、疾病建模和药物筛选等。
