The shortcomings of insulin therapy for Type 1 diabetes (T1D) can be improved by providing a new insulin-producing source to the patients, which regulates the glucose levels from minute-to-minute. Despite great successes have been achieved following the groundbreaking publication of the Edmonton protocol and infusion of islets into the portal vein, islet transplantation is not yet a widely applied treatment for T1D. The reasons for this are multifactorial, but the mandatory use of life-long immunosuppression to prevent graft rejection plays an important role. A promising approach to prevent the use of immunosuppression is the encapsulation of insulin-producing cells in semipermeable and immunoprotective membranes, also called immunoisolation. Although immunoisolation has shown to be effective in curing T1D, graft survival was limited to several months in most studies, which restricts its clinical application. Associated factors for the low survival rate are oxidative and inflammatory stress-induced graft loss and insufficient oxygen/nutrient supply caused by peri-capsular fibrotic overgrowth. The dietary fiber pectin might improve both limiting factors as it possesses the ability to support cell function and modulate immune responses. Here, we show that dietary pectin also has direct beneficial effects on islets, as well as the fermentation products of pectin. Addition of low DM-pectin to the intracapsular environment and on the surface of the capsule supports encapsulated islet graft survival and prevents fibrotic overgrowth. In this thesis, we present new insight in the pectin mechanism contributing to the management of diabetes and present novel applications of pectins as immunomodulatory and cell-protective biomaterial.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2021|