Benutzerspezifische Werkzeuge

Objectives/Aims

In this project, we will pursue the following three objectives:

(I) Localization and characterization of islet morphology, vascularization, proliferation, and oxidative stress after intra-adrenal transplantation in a large animal model (Ludwig/Morawietz). 

Porcine islets will be isolated and transplanted into the adrenal gland of healthy Goettingen minipigs. As intra-individual control, islets from the same preparation will be transplanted into the right liver lobe of the same animal. After 4 weeks, the graft bearing organs will be retrieved and the islet graft will be analysed for viability, apoptosis, proliferation, vascularization and markers of oxidative stress in the adrenal and liver, respectively. 

(II) Therapeutic potential of intra-adrenal transplantation of pancreatic islets in a large animal diabetes model and effects on adrenal function (Ludwig/Bornstein).

Porcine islet preparations will be transplanted into the adrenal of diabetic minipigs. Graft function will be evaluated by close metabolic follow up including blood glucose monitoring (continuous glucose monitoring systems; CGMS) and glucose tolerance tests. To determine effects of intra-adrenal islet transplantation on the adrenergic axis, animals will be analysed by ACTH and glucagon test. Healthy controls will be tested in parallel. 

(III) Analysis of immunosuppressive potential of the adrenal microenvironment in an allogeneic islet transplantation model (Ludwig).

In order to evaluate the immunosuppressive potential of the intra-adrenal transplantation site, allogeneic islets will be transplanted into diabetic immune-competent mice either into the adrenal or underneath the kidney capsule, respectively. Animals will be followed metabolically to determine the time period until graft rejection occurs. Graft bearing organs will be recovered and assessed by immunohistochemistry for rejection markers.