An in vivo model of pancreatic islet organoids. In type I diabetes the insulin-producing beta cells of the pancreatic islets are being destroyed through an autoimmune process, necessitating lifelong insulin injections to maintain adequate insulin levels, and prevent health problems from diabetes. A more physiologic insulin production might become possible through transplantation of pancreatic islets. For the experiments proposed here, a basement membrane extract will be used to keep the transplanted islets in good condition and alive. Also, the autoimmune process (which involves T cells) can be studied more closely in such an artificial pancreatic islet organ (organoid) because the components of the organ, the single islets, are assembled to form a new organ. This proposal has therefore 3 aims: (1) To first destroy pancreatic beta cells in an immunodeficient strain of mice NOD/LtSz- scid/scid with a chemical (streptozotocin) in order to make them diabetic and to then transplant these diabetic, immunodeficient mice with healthy islets from another mouse strain. (2) After the organoid transplant, the organoids will not be rejected because the mice are immunodeficient, and their diabetes should improve because of the new islets. The mice will be monitored for possible improvement in their diabetes. The organoids will be characterized with various methods for the survival and function of insulin-producing beta cells [by using (laser (confocal) microscope and molecular techniques to detect pancreatic insulin-producing cells) to learn more about the conditions that influence the outcome of the transplantation procedure. (3) Lastly, certain mice that develop diabetes naturally [the non-obese diabetic (NOD) strain] will be transplanted with NOD pancreatic islet organoids. We will investigate whether the autoimmune process that usually leads to the disease, attacks the transplanted cells organoid, using different techniques [molecular techniques for the T-cell receptor, laser microscope].
| Onengut-Gumuscu, S; Ewens, K G; Spielman, R S et al. (2004) A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun 5:678-80 |
