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.
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.
|Klueh, Ulrike; Czajkowski, Caroline; Ludzinska, Izabela et al. (2016) Impact of CCL2 and CCR2 chemokine/receptor deficiencies on macrophage recruitment and continuous glucose monitoring in vivo. Biosens Bioelectron 86:262-9|
|Klueh, Ulrike; Qiao, Yi; Frailey, Jackman T et al. (2014) Impact of macrophage deficiency and depletion on continuous glucose monitoring in vivo. Biomaterials 35:1789-96|
|Klueh, Ulrike; Antar, Omar; Qiao, Yi et al. (2014) Role of vascular networks in extending glucose sensor function: Impact of angiogenesis and lymphangiogenesis on continuous glucose monitoring in vivo. J Biomed Mater Res A 102:3512-22|
|Klueh, Ulrike; Frailey, Jackman T; Qiao, Yi et al. (2014) Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring. Biomaterials 35:3145-53|
|Klueh, Ulrike; Antar, Omar; Qiao, Yi et al. (2013) Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo. J Diabetes Sci Technol 7:1538-46|
|Klueh, Ulrike (2013) Analysis: on the path to overcoming glucose-sensor-induced foreign body reactions. J Diabetes Sci Technol 7:452-4|
|Klueh, Ulrike; Kaur, Manjot; Qiao, Yi et al. (2010) Critical role of tissue mast cells in controlling long-term glucose sensor function in vivo. Biomaterials 31:4540-51|
|Klueh, Ulrike; Liu, Zenghe; Feldman, Ben et al. (2010) Importance of interleukin-1 and interleukin-1 receptor antagonist in short-term glucose sensor function in vivo. J Diabetes Sci Technol 4:1073-86|