Diabetes type 1 is an autoimmune disease in which the patient’s own immune systemdestroys the insulin producing β-cells, located in the pancreatic islets. Without enough insulinproduction, the blood glucose levels of the patient rise, which can lead to damages of bloodvessels and nerves, blindness or even seizures and comas. For some patients that havetrouble maintaining normoglycaemia allogeneic islet transplantation has become analternative treatment option. Patients with these transplanted islets are no longer prone tohypoglycaemic episodes and can sometimes become completely insulin independent.However, this success is not long-lived. The life span of the transplanted islets is limited dueto the host’s immune responses and the toxicity of modern immunosuppressive agents. Inthis thesis, islet encapsulation for clinical transplantation is investigated and furtherdeveloped. Islet encapsulation can protect the islets from the immune system, without theaid of the immunosuppressants. The construction and optimization of a micro-encapsulatorthat can be used to create encapsulations is described, as well as the multiple parameters tocreate small, uniform encapsulations. To further enhance the biocompatibility andimmunoprotective properties of alginate hydrogel, alginate was purified to eliminate mostof the impurities and tested for its permeability. Encapsulating pancreatic islets in thispurified alginate showed encouraging results, with the islets remaining viable and functionallonger than their control counterparts. Larger islets can develop necrotic cores withinencapsulations, due to the lack of vascularization. To create smaller islets out of dissociatedlarger islets, a single-step encapsulation and aggregation method was developed, thatunfortunately was not suitable for islet cells, but was capable of developing functionalhepatic organoids out of HepaRG cells, that could be used for drug testing. Finally, a proof ofprinciple was given for the creation of pancreatic islet patches using 3D bioprinting methods.
| Date of Award | 17 May 2019 |
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| Original language | English |
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| Awarding Institution | - University Of Strathclyde
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| Sponsors | University of Strathclyde |
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| Supervisor | Will Shu (Supervisor) & Mary Grant (Supervisor) |
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