Macrophages and Biosensor Function in Vivo

体内巨噬细胞和生物传感器功能

• 批准号: 8461271
• 负责人: DON KREUTZER
• 金额: $ 42.89万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8461271
• 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.

描述（由申请人提供）：糖尿病是一个真正的“沉默杀手”，其人力和经济成本，以美国，这个世界被大大低估了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。仅在2007年，糖尿病估计花费了美国1740亿美元。预防或至少最大限度地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，在预防糖尿病的毁灭性并发症和经济成本方面拥有最大的希望。不幸的是，长期植入式葡萄糖传感器的开发在很大程度上受到植入式传感器的生物污染的阻碍，生物污染是由与传感器诱导的“异物反应”相关的组织反应引起的，包括炎症、纤维化和血管退化。包括巨噬细胞（MQ）、树突状细胞（DC）和多核巨细胞（GC）在内的单核细胞相关细胞（MRC）在控制炎症、血管生成、纤维化和“异物反应”中的血管消退中的关键作用在各种疾病和可植入生物材料中得到充分确立。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中的作用仍有待研究。本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，而且还开发了通过靶向传感器植入部位的巨噬细胞及其产物来延长葡萄糖传感器体内寿命的策略和工具。

项目成果

Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo.

IL-1/IL-1受体拮抗剂家族细胞因子在体内长期连续血糖监测中的作用。

• DOI: 10.1177/193229681300700614
• 发表时间: 2013
• 期刊: Journal of diabetes science and technology
• 影响因子: 5
• 作者: Klueh,Ulrike;Antar,Omar;Qiao,Yi;Kreutzer,DonaldL
• 通讯作者: Kreutzer,DonaldL

Role of vascular networks in extending glucose sensor function: Impact of angiogenesis and lymphangiogenesis on continuous glucose monitoring in vivo.

• DOI: 10.1002/jbm.a.35031
• 发表时间: 2014-10
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
• 影响因子: 4.9
• 作者: Klueh, Ulrike;Antar, Omar;Qiao, Yi;Kreutzer, Donald L.
• 通讯作者: Kreutzer, Donald L.

Analysis: on the path to overcoming glucose-sensor-induced foreign body reactions.

分析：克服葡萄糖传感器引起的异物反应的途径。

• DOI: 10.1177/193229681300700222
• 发表时间: 2013
• 期刊: Journal of diabetes science and technology
• 影响因子: 5
• 作者: Klueh,Ulrike

Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo.

• DOI: 10.1016/j.bios.2016.06.026
• 发表时间: 2016-12-15
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Klueh, Ulrike;Czajkowski, Caroline;Ludzinska, Izabela;Qiao, Yi;Frailey, Jackman;Kreutzer, Donald L.
• 通讯作者: Kreutzer, Donald L.

Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring.

• DOI: 10.1016/j.biomaterials.2014.01.001
• 发表时间: 2014-03
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Klueh, Ulrike;Frailey, Jackman T.;Qiao, Yi;Antar, Omar;Kreutzera, Donald L.
• 通讯作者: Kreutzera, Donald L.