Thesis summarized by Dr. Schive

In type 1 diabetes the beta cells are lost and can no longer synthesize the vital hormone insulin. Islet allotransplantations can replace the lost beta cells. In this thesis we describe the state of this treatment in Norway by reporting the cost and clinical outcome for patients transplanted at our center in Oslo between 2010 – 2015. We compare our results to other centers and find similar results for graft function and disease modification, and we highlight areas that can be further improved. We also present the first documented pregnancy after islet allotransplantation, with a successful outcome for both the pregnancy and the transplanted graft. This is of particular relevance as many of the potential recipients are females in their fertile age.

Despite an increasing experience with islet transplantations worldwide, outcomes after transplantation remains variable. Adipose tissue-derived stromal cells (ASCs) have been shown to positively affect islets. In this thesis we describe how soluble mediators released by human ASCs affect human islet viability in vitro, and how exposing ASCs to a hypoxic environment increase the release of islet trophic factors and decrease the levels of detrimental factors. We also show how preconditioning ASCs in hypoxia improve their therapeutic efficiency in a mouse diabetes model. Finally, we describe a method for large scale production of ASCs using automated systems, a workflow that could be used for future clinical trials.

Combining these elements, we describe both the present situation of islet allotransplantation in Norway, and a possible route for improving outcome in the future.

Public Defence: Simen W. Schive - Institute of Clinical Medicine (uio.no)