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

一种抑制细胞间通讯的新型流体和膜平台

• 批准号: 9169632
• 负责人: Dana M Spence
• 金额: $ 36.82万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169632
• 关键词: 3-Dimensional; 3D Print; Affect; Affinity; Agonist; Amino Acids; Animal Model; Bacteria; Beta Cell; Biological; Biological Assay; Blindness; Blood; Blood Circulation; Blood Platelets; Blood Vessels; Blood flow; C-Peptide; California; Cell Communication; Cell Line; Cell secretion; Cells; Chemicals; Clinical Research; Communication; Complications of Diabetes Mellitus; Data; Development; Devices; Diabetes Mellitus; Diagnosis; Diet; Disease; Disulfides; Endothelial Cells; Endothelium; Erythrocytes; Formulation; Health; Human; In Vitro; Individual; Injection of therapeutic agent; Insulin; Insulin-Dependent Diabetes Mellitus; Intravenous; Ions; Kidney Diseases; Knock-out; Laboratory Research; Measures; Membrane; Methods; Microfluidic Microchips; Modeling; Modification; Molecular; Nerve; Neuropathy; Organ; Pancreas; Pathway interactions; Peptides; Pharmacotherapy; Phase; Physical activity; Pilot Projects; Placebos; Printing; Rattus; Replacement Therapy; Retinal Diseases; Role; Running; Signal Pathway; Signaling Molecule; Small Interfering RNA; Stream; Structure of beta Cell of islet; Technology; Therapeutic; Tissues; Travel; United States; Work; base; granule cell; improved; in vivo; inhibitor/antagonist; innovation; intercellular communication; intravenous injection; knock-down; knockout animal; novel; small molecule; theories; therapy development; tool

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.

项目摘要 微流体装置已经成功地用于生物测定，特别是用于涉及以下的测定： 细菌和细胞。虽然涉及细菌和细胞的重要研究仍在进行中， 在研究实验室中，现在正在开发许多设备，使得组织甚至器官可以被移植。 在这些设备上培养，以进行更真实的生物学研究。近十年来，PI一直是 在微流控装置中培养内皮细胞并研究内皮细胞（如 血管壁组织）与诸如红细胞（RBC）的血液成分的流动流， 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（胰腺细胞，负责分泌众所周知的生物活性物质的细胞）， 肽，胰岛素）。本申请的主要目标之一是测量和理解细胞间的 以及血管细胞、血流和血管壁之间的组织间通讯 （内皮）。不幸的是，已经表明，通过敲除或敲低来影响β-细胞， 方法通常会对整个细胞产生不利影响，因此难以区分关键因素， 生物学途径。在这个应用程序中，调查小组将开发一个新的平台， 具有选择性捕获的改性孔的容纳膜插入物的流体装置的3D打印 分子信使通过血流从一个组织到另一个组织。我们还将 开发一种新的，使静脉注射（IV）药物治疗的候选人到一个流动的流 血液或血液成分以将结果桥接到使用1型动物模型的完整体内研究中 糖尿病（T1 D）。我们假设，这种研究细胞间和细胞间相互作用的新平台的开发， 组织间通讯可用作体内研究的桥梁， T1 D患者的替代疗法。