UC Irvine

An estimated 1.25 million Americans suffer from type 1 diabetes (T1D), an incurable autoimmune disease with increasing prevalence. Currently, patients manage their disease with combined insulin administration via injection or pump and blood glucose monitoring. For severe cases, pancreatic islet transplantation into the liver via the portal vein has shown to increase patient quality of life; however, this procedure comes with many risks and potential morbidities making it unsuitable for a majority of the T1D population. A bioartificial pancreas provides an attractive advantage over current treatment methods by allowing “hands-free” glucose control mediated by pancreatic islets.

We developed a two-phase approach to islet transplantation with a thin-sheet device perfused by the host vasculature prior to islet introduction. In phase one, the host develops new tissue within the device that is fully integrated into the subcutaneous space, demonstrated by infiltration of mature vasculature via both lectin perfusion and histology as well as nerve tissue via histology. Noninvasive in vivo oxygen dynamics measurements indicate shorter prevascularization periods may be more beneficial. In phase two, we infuse islets with a newly developed loading method into a single file configuration within the device channels such that they are immediately adjacent to host vasculature. Prototype devices were fabricated, modified, and tested in diabetic athymic nude mice. Devices were allowed to vascularize and then re-accessed to load islets in situ. Intraperitoneal glucose tolerance tests, C-peptide measurements, nonfasting blood glucose values, and immunohistochemistry staining results indicate islets transplanted into devices maintain partial function and in a few cases, euglycemia. Device modeling with in vivo perfusion conditions indicates the islet packing fraction and level of perfusion majorly contribute to insulin production by the device and could explain differences in glycemic control.