Macrophages and Biosensor Function in Vivo

体内巨噬细胞和生物传感器功能

• 批准号: 7656525
• 负责人: DON KREUTZER
• 金额: $ 47.31万
• 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/7656525
• 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; 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; public health relevance; 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”，其对美国的人力和经济成本以及世界的重视程度很高。糖尿病的主要并发症包括心脏病，中风，高血压，肾脏疾病，失明，神经系统损害和截肢。因此，糖尿病代表了美国第五大疾病。仅在2007年，糖尿病就被估计耗资1740亿美元。防止或至少最小化糖尿病并发症的关键是血糖控制。可植入的葡萄糖传感器（包括基于传感器的闭环系统）拥有防止糖尿病的毁灭性并发症和经济成本的最大前景。不幸的是，长期植入葡萄糖传感器的发展很大程度上通过与传感器诱导的“异物反应”相关的组织反应（包括炎症，纤维化，纤维化，血管回归）对植入的传感器进行生物结构。单核细胞相关细胞（MRC）在内的关键作用包括巨噬细胞（MQS），树突状细胞（DCS）和多核巨细胞（GCS）在控制“异物反应”中的炎症，血管生成，纤维化和血管回归中的关键作用在各种疾病中良好地建立了各种疾病和动物反应中的血管生成，纤维化和血管回归。尽管已知MRC存在于传感器植入部位，但通过控制组织，这些细胞直接控制传感器功能（传感器的生物汇合）和/或间接地控制组织中的作用，反应（炎症，血管生成和纤维化）仍然可以解剖。这项研究的目的不仅是确定MRC及其产物对传感器功能的体内损失的贡献，而且还要开发可以通过靶向巨噬细胞及其产物在传感器植入的位点来扩展葡萄糖传感器寿命的策略和工具。公共卫生相关性：葡萄糖传感器被认为是糖尿病患者长期葡萄糖管理的最大希望。不幸的是，当前可植入的葡萄糖传感器仅在传感器功能失去的几天内持续几天，这在很大程度上归因于组织炎症。我们目前的建议集中于确定巨噬细胞在体内失去传感器功能的巨噬细胞的作用。这些研究的结果不仅可能会对巨噬细胞在体内的葡萄糖传感中的作用有了新的了解，而且很可能会提供新的工具来控制体内和延长体内植入式传感器寿命。