Imaging islets in implantable microcapsules

Ut Southwestern Medical Center, Dallas TX

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Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] 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. [unreadable] 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. [unreadable] [unreadable]