Impairment and destruction of beta cells by an autoimmune attack leads to the onset of hyperglycemia in type 1 diabetes (T1D). However, knowledge on changes in islet cell physiology leading to dysfunction, failure and death of the cells is incomplete. This is partially due to technical limitations which do not allow the study of islet function within intact pancreatic tissue, but rely on the enzymatic isolation of islets. During isolation islets suffer from enzymatic and mechanical stress. After isolation the islets are separated from their surrounding tissue, including most of the infiltrating cells. In addition, enzymatic isolation of structurally damaged islets is challenging and hampers the study of islet physiology in T1D.

Our project aims to establish a pancreas tissue slice platform for the study of human islet physiology in the pathogenesis of T1D. Pancreas tissue slices allow the study of islet physiology in an intact environment in situ, avoiding isolation stress and separation from their surroundings. In rodents pancreas tissue slices have been successfully used to study rodent islet biology under various conditions. We recently established the pancreas tissue slice platform using human pancreas. We plan to establish this technique at the Diabetes Research Institute, University of Miami, and at the nPOD Organ Processing and Pathology Core, University of Florida. This will enable the use of pancreas tissue slices for the ex-vivo study and functional assessment of nPOD pancreata. Furthermore, we aim to develop an organotypic culture platform to allow investigating human islets within intact pancreatic tissue over several days. Finally, we will assess the feasibility of this culture platform by using exposure to viruses as a model system to explore effects on islet cell pathophysiology. We believe combination of this unique network with our novel approach will facilitate new insight into the pathogenesis of diabetes. Of note, this platform will empower additional studies to be conducted, beyond those described here. This effort is conceived as a collaborative working group effort which will seek support from the Helmsleüy Charitable Trust George Eisenbarth nPOD Award for Team Science.