The Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors with Diabetes (nPOD) Program: goals, operational model and emerging findings

Type 1 diabetes (T1D) is considered an autoimmune disease, predominantly mediated by autoreactive T cell responses, which over time leads to the destruction of pancreatic beta cells and insulin deficiency. Symptoms often appear in childhood or adolescence, but the disease can develop in adult patients as well (1). Both therapeutic management and clinical outcomes have dramatically improved during the last few decades, yet T1D remains a major cause of suffering, a burden to society, and its incidence appears to be increasing, especially in younger children (2). Although we can identify individuals at increased risk among patients' relatives, the disease cannot be prevented and there is no definitive cure (3). Pancreas and islet transplantation can restore insulin independence, at least for a period of time, but are not universally available and require chronic immunosuppression (4). The partial success of human clinical trials aimed at ameliorating islet autoimmunity likely reflects our incomplete knowledge of etiological factors and the limited understanding of the key pathogenic mechanisms that cause the disease (1, 3). Our ability to study the disease has been hampered by scarce access to the pancreas and other disease-related tissues. The limited data available from studies of human pancreata from patients have been to a large extent, from pancreata obtained several decades ago that were not studied with modern technologies. Furthermore, they may no longer reflect current disease, particularly as they relate to etiological factors if these vary over time. Our views of the disease pathogenesis have been largely shaped by studies in experimental rodent models of the disease, especially the non-obese diabetic (NOD) mouse (5). Yet critical questions regarding disease pathogenesis are specific to humans and cannot be easily investigated in experimental animals. Among these are: (i) the nature (phenotypically and functionally) of autoreactive T and B cells, which may be therapeutically targeted; (ii) the role of viral infections, which could perhaps be averted by vaccination if responsible viruses were definitively identified; (iii) potential pathways of beta cell regeneration; and (iv) additional hitherto undefined pathogenic mechanisms. Thus, there is a clear need to study human pancreata and related tissues from T1D patients. Such efforts could identify novel therapeutic targets and define possible strategies for combinatorial therapies that target multiple disease pathways, both immune and non-immune related. In 2007, the JDRF recognized such a need and supported the creation of the JDRF Network for the Pancreatic Organ Donors with Diabetes (JDRF nPOD; www.JDRFnPOD.org). This article describes nPOD's operational model and some recent preliminary and novel findings that have emerged from research studies utilizing nPOD specimens.