Imaging islets in implantable microcapsules

描述(由申请人提供)： 我们研究项目的总体目标是开发能够有效包裹单个胰岛的立方体微胶囊。微囊的三个正交表面将是纳米多孔的，以免疫保护胰岛细胞免受宿主的伤害，同时允许被包裹的胰岛细胞和宿主之间自由交换营养物质、废物、葡萄糖和胰岛素。三个纳米孔表面也将是透明的，以便光学地探测包裹的胰岛的钙离子通量和线粒体对葡萄糖的反应，并检验包裹不影响胰岛功能的假设。在其他三个表面，我们将安装用于MRI的射频(RF)传感器。我们将使用MRI来成像胰岛功能，使用基于激活的对比剂锰的摄取。我们将检验这一假设，即胰岛功能和生存能力可以通过MRI、后封装进行评估。 我们方法的优势在于，我们可以提供目前在包埋式胰岛细胞治疗中难以捉摸的元素：1)通过非常好地控制包埋式设备的孔隙率来保护胰岛免受宿主的免疫保护，这是使用曲折的聚合物无法实现的；2)大的表面积与体积比，为单个胰岛提供氧气和营养，这是目前基于MEMS的生物胶囊无法实现的；3)通过光学方法直接对包封式胰岛的生存能力进行成像；以及4)对包封式胰岛进行直接、非侵入性的、周期性的和功能性成像。我们的方法可以很容易地封装任何天然或转基因的贝塔细胞，我们的设备可能会安装过多的传感器来测量体内的氧气、pH、温度和其他环境条件。

DESCRIPTION (provided by applicant): The overall goal of our research project is to develop cubic microcapsules that can effectively encapsulate individual islets. Three orthogonal surfaces of the microcapsules will be nanoporous, to immunoprotect the islet cells from the host while allowing the free exchange of nutrients, waste products, glucose and insulin between the encapsulated islet cells and the host. The three nanoporous surfaces will also be transparent so as to optically probe the encapsulated islet's calcium fluxes and mitochondrial response to glucose, and test the hypothesis that encapsulation does not affect islet function. On the other three surfaces, we will mount radio frequency (RF) sensors for MRI. We will use MRI to image islet function using activation-based uptake of the contrast agent manganese. We will test the hypothesis that islet function and viability can be assessed through MRI, post encapsulation. The strength of our approach is that we can provide elements that are currently elusive in encapsulated islet cell therapy: 1) immunoprotection of islets from the host through extremely well-controlled porosity of the encapsulation device, not achieved with tortuous polymers, 2) a large surface-to-volume ratio that provides oxygen and nutrients to the individual islets, not achieved with present day MEMS based biocapsules, 3) direct imaging of the viability of encapsulated islets through optical methods, and 4) direct, noninvasive, periodic and functional imaging of the encapsulated islets. Our approach can be easily adapted to encapsulate any native or genetically modified beta cells, and our devices may be mounted with a plethora of sensors to measure oxygen, pH, temperature and other environmental conditions in vivo.