Macrophages and Biosensor Function in Vivo

体内巨噬细胞和生物传感器功能

• 批准号: 8067133
• 负责人: DON KREUTZER
• 金额: $ 44.4万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8067133
• 关键词: Amputation; Bacteria; Biocompatible Materials; Biosensor; Blindness; Blood Vessels; Cells; Complications of Diabetes Mellitus; Cytokine Network Pathway; Data; Dendritic Cells; Development; Diabetes Mellitus; Diabetic mouse; Disease; Fibrosis; Foreign-Body Reaction; Future; Giant Cells; Glucose; Goals; Health; Heart Diseases; Human; Hypertension; In Vitro; Inflammation; Inflammatory; Kidney Diseases; Knowledge; Leukocytes; Literature; Location; Longevity; Mus; Nervous System Trauma; Patients; Pharmaceutical Preparations; Play; Reaction; Reagent; Research; Role; Site; Stroke; System; Testing; Therapeutic Intervention; Tissues; Transgenic Mice; United States; angiogenesis; base; cost; cytokine; design; economic cost; glucose sensor; glycemic control; human disease; implantation; implanted sensor; in vivo; macrophage; microorganism; monocyte; mouse model; mutant; non-diabetic; novel; novel therapeutic intervention; prevent; sensor; tool; vessel regression

DESCRIPTION (provided by applicant): Diabetes is truly a "silent killer", whose human and economic costs to the U.S., and the world is vastly under-appreciated. Major complications of diabetes include heart disease, stroke, high blood pressure, kidney disease, blindness, nervous system damage, and amputations. As such, diabetes represents the fifth-deadliest disease in the United States. In 2007 alone, diabetes was estimated to cost the U.S. $174 billion dollars. The key to preventing or at least minimizing the complications of diabetes is glycemic control. Implantable glucose sensors, including sensor based closed loop systems, hold the greatest promise for preventing the devastating complications and economic costs of diabetes. Unfortunately, the development of long-term implantable glucose sensors has been hampered in large part by bio-fouling of the implanted sensor by the tissue reactions associated with sensor-induced "foreign body reactions", including inflammation, fibrosis and vessel regression. The key role of Monocyte Related Cells (MRCs) including macrophages (MQs), dendritic cells (DCs), and multi-nucleated giant cells (GCs) in controlling inflammation, angiogenesis, fibrosis and vessel regression in "foreign body reactions" is well established in a variety of diseases and implantable biomaterials. Although MRCs are known to be present at sites of sensor implantation, the roles of these cells in controlling sensor function directly (biofouling of sensor) and/or indirectly by controlling tissue, reactions (inflammation, angiogenesis and fibrosis) remain to be dissected. The goal of this research is not only to determine the contribution of MRCs and their products to the in vivo loss of sensor function, but also to develop strategies and tools that can extend glucose sensor lifespan in vivo by targeting macrophages and their products at sites of sensor implantation. PUBLIC HEALTH RELEVANCE: Glucose sensors are considered the greatest hope for long-term glucose management for patients with diabetes. Unfortunately, current implantable glucose sensors last for only a few days before sensor function is lost due in large part to tissue inflammation. Our present proposal is focused on determining the role of macrophages, a key inflammatory cell, in this lost of sensor function in vivo. The results of these studies will likely not only provide a new understanding of the role of macrophages in glucose sensing in vivo, but will likely give new tools to control macrophages in vivo and prolong implantable sensor lifespan in vivo.

描述（由申请人提供）：糖尿病确实是一个“沉默的杀手”，其给美国和世界造成的人员和经济损失被大大低估。糖尿病的主要并发症包括心脏病、中风、高血压、肾病、失明、神经系统损伤和截肢。因此，糖尿病是美国第五大致命疾病。仅 2007 年一年，糖尿病就给美国造成了 1740 亿美元的损失。预防或至少减少糖尿病并发症的关键是血糖控制。植入式葡萄糖传感器，包括基于传感器的闭环系统，在预防糖尿病的破坏性并发症和经济成本方面具有最大的前景。不幸的是，长期植入式葡萄糖传感器的发展在很大程度上受到与传感器引起的“异物反应”相关的组织反应（包括炎症、纤维化和血管退化）对植入传感器的生物污染的阻碍。单核细胞相关细胞 (MRC) 包括巨噬细胞 (MQ)、树突状细胞 (DC) 和多核巨细胞 (GC) 在控制“异物反应”中的炎症、血管生成、纤维化和血管退化方面的关键作用已得到充分证实在多种疾病和可植入生物材料中。尽管已知 MRC 存在于传感器植入部位，但这些细胞在直接控制传感器功能（传感器的生物污染）和/或通过控制组织反应（炎症、血管生成和纤维化）间接控制传感器功能方面的作用仍有待深入研究。这项研究的目标不仅是确定 MRC 及其产物对体内传感器功能丧失的贡献，而且还开发策略和工具，通过靶向巨噬细胞及其产物，延长体内葡萄糖传感器的寿命。传感器植入。公众健康相关性：葡萄糖传感器被认为是糖尿病患者长期血糖管理的最大希望。不幸的是，目前的植入式葡萄糖传感器只能持续几天，传感器功能在很大程度上会因组织炎症而丧失。我们目前的建议重点是确定巨噬细胞（一种关键的炎症细胞）在体内传感器功能丧失中的作用。这些研究的结果可能不仅会提供对巨噬细胞在体内葡萄糖传感中的作用的新认识，而且可能会提供新的工具来控制体内巨噬细胞并延长体内植入式传感器的寿命。