A Novel Fluidic and Membrane-based Platform for Inhibiting Intercellular Communication

项目总结 微流控装置已成功地应用于生物检测，特别是对 细菌和细胞。虽然涉及细菌和细胞的重要研究仍在进行中，但许多 研究实验室，现在正在开发许多设备，使得组织，甚至器官，可以 在这些设备上培育，以进行更现实的生物学研究。近十年来，PI一直在 微流控培养内皮细胞及其与血管内皮细胞相互作用的研究 血管壁组织)具有流动的血液成分流，例如红细胞(RBCs)和 血小板。在本申请中，调查小组希望扩展这些组织，以包括 胰腺组织的组成部分(-细胞，负责分泌众所周知的生物 多肽、胰岛素)。这个应用程序的主要目标之一是测量和理解细胞间 以及细胞、血流和血管壁之间的组织间通讯 (内皮细胞)。不幸的是，已经表明通过基因敲除或基因敲除来影响-细胞 方法通常会对整个细胞产生不利影响，因此很难区分 生物途径。在这一应用中，调查团队将开发一个基于 3D打印容纳具有经修改的孔的膜插件的流体设备，所述修改的孔选择性地捕获 分子信使通过血液从一个组织传递到另一个组织。我们还将 开发一种新的能够将候选药物静脉(IV)注射到流动的 使用1型动物模型将结果连接到完整的体内研究中的血液或血液成分 糖尿病(T1D)。我们推测，这一新型细胞间研究平台的开发 组织到组织的交流可以作为体内研究的桥梁，涉及可能的额外 T1D患者的替代疗法。

PROJECT SUMMARY Microfluidic devices have been successfully used in biological assays, especially for assays involving bacteria and cells. While important studies involving bacteria and cells are still in progress in many research laboratories, many devices are now being developed such that tissues, and even organs, can be cultivated on these devices for more realistic biological studies. For nearly a decade, the PI has been culturing endothelial cells in microfluidic devices and investigating the interactions of the endothelium (as a vessel wall tissue) with a flowing stream of blood components such as red blood cells (RBCs) and platelets. In this application, the investigative team wishes to expand upon these tissues to include components of pancreatic tissue (-cells, the cells responsible for secreting the well-known biological peptide, insulin). One of the major objectives of this application is to measure and understand cell-to-cell and tissue-to-tissue communication between the -cells, the bloodstream, and the vessel wall (endothelium). Unfortunately, it has been shown that affecting -cells by knockout or knockdown approaches often adversely affects the cell as a whole, thus making it difficult to distinguish key factors in the biological pathways. In this application, the investigative team will develop a novel platform based on 3D-printing of fluidic devices hosting membrane inserts with modified pores that selectively captures molecular messengers traveling through the bloodstream from one tissue to another. We will also develop a new that enables intravenous (IV) injections of drug therapy candidates into a flowing stream of blood or blood components to bridge results into a full in vivo study using animal models of type 1 diabetes (T1D). We hypothesize that the development of this novel platform for studying cell-to-cell and tissue-to-tissue communication can be used as a bridge to in vivo studies involving a possible additional replacement therapy for people with T1D.