Impact of the Vascular System and CGM

增加血管(BV)密度和接近葡萄糖传感器的概念增加了实时间质 体内的葡萄糖水平和传感器功能是被接受的，尽管支持这一概念的实验数据有限。 目前，文献中没有关于淋巴管(LV)的作用的数据，甚至没有猜测 BV和LV联合应用增强体内感受器功能。同样，人们对调解人和 这些机制涉及传感器植入部位这些血管网络的形成和功能。新近基因 我们实验室的治疗研究表明：1)基于血管内皮生长因子-A的局部基因治疗增加了血管 葡萄糖传感器植入部位的网络(血管和淋巴管)；和2)这种局部增加 血管网络增强和扩展了体内葡萄糖传感器的功能，从传感器后7天延长到28天以上 植入。这一令人兴奋的数据提供了“概念证据”，即增加血糖传感器部位的血管网络 植入可提高连续血糖监测(CGM)的性能。 这些数据引出的关键问题包括：1)控制的关键细胞、中介和机制(S)是什么 传感器植入部位的血管网络(血管(BV)和淋巴管(LV))2)它们如何控制 CGM；3)BV、LV或血管网络的组合对增强和扩大体内CGM至关重要；4)什么 炎症和纤维化在控制传感器植入部位的血管网络中的作用，以及5)可以 增强型细胞外基质(ECM)用于控制血管网络的形成、增强和延伸 用于经皮和完全植入型葡萄糖传感器的CGM？ 这一应用的三个主要研究目标是：1)开发和验证基于ECM的传感器涂层 药物输送能力，以控制炎症，纤维化和促进血管网络的形成 2)测定BV、LV和BV+LV对正常和糖尿病小鼠组织反应和CGM的影响 小鼠；3)表征控制血管生成、淋巴管生成的细胞、介体和途径 传统和激光捕获显微外科技术和传感器植入部位的组织并与 CGM糖尿病状态。

The concept that increasing blood vessel (BV) density and proximity to glucose sensors increases real time interstitial glucose levels and sensor function in vivo is accepted, despite limited experimental data to support that concept. Currently there is no previous data or even conjecture in the literature on the role of lymphatic vessels (LV) or the combinations of BV & LV in enhancing sensor function in vivo. Likewise nothing is known about the mediators and mechanisms involved in the formation and function of these vascular networks at sensor implantation sites. Recent gene therapy studies in our laboratories have demonstrated that 1) VEGF-A based local gene therapy increases vascular networks (blood vessels and lymphatic vessels) at sites of glucose sensor implantation; and 2) this local increase of vascular networks enhances and extends glucose sensor function in vivo from 7 days to greater than 28 days post sensor implantation. This exciting data provides "proof of concept" that increasing vascular networks at sites of glucose sensor implantation enhances performance of continuous glucose monitoring (CGM). Among the key questions that this data leads to is: 1) what are the key cells, mediators and mechanism(s) that control vascular networks (blood vessels (BV) and lymphatic vessels (LV)) at sites of sensor implantation; 2) how do they control CGM; 3) are BV, LV or the combination of vascular networks critical to enhancing and extending CGM in vivo; 4) what is the role of inflammation and fibrosis in controlling vascular networks at sensor implantation sites, and 5) can bio- enhanced extracellular matricies (ECM) be developed to control vascular network formation and enhance and extend CGM for both transcutaneous and totally implantable glucose sensors? The 3 major research goals for this application are: 1) develop and validate ECM based sensor coatings with drug delivery capability to control inflammation, fibrosis and promote vascular network formation in normal and diabetic mice; 2) determine the impact of BV, LV and BV+LV on tissue reactions and CGM in normal and diabetic mice; 3) characterize the cells, mediators and pathways that control angiogenesis, lymphangiogenesis using traditional and laser capture microsurgery technology and tissue from sensor implantation sites and correlate with CGM diabetic status.