Background
The Network for Pancreatic Organ donors with Diabetes was established to recover and characterize pancreata and related organs from cadaveric organ donors with various risk levels for type 1 diabetes (T1D). These biospecimens are available to investigators for collaborative studies aimed at addressing questions related to TID natural history and pathogenesis.
Research design and methods
Organ donors included T1D patients (new-onset to long-term), non-diabetic autoantibody positive subjects, non-diabetic controls, and individuals with disorders relevant to β-cell function. Pancreas recovery and transport met transplant-grade criteria. Additional samples recovered included serum, whole blood, spleen, and pancreatic and non-pancreatic lymph nodes. Biospecimens were processed for cryopreserved cells, fixed paraffin and fresh frozen blocks, and snap frozen samples. T1D autoantibodies, c-peptide levels, and high-resolution HLA genotyping for risk alleles were also determined.
Results
Over 160 donors have been enrolled (ages of 1 day to > 90 years). Standard operating procedures were established along with a quality management system. Donor demographics, laboratory assays, and histopathological characterizations were shared through an open online informatics system. Biospecimens were distributed to more than 60 investigators.
Conclusions
The nPOD program provides access to high quality biospecimens without cost to investigators. Collaborations and open data sharing are emphasized to maximize research potential of each donor. Based on initial successes, the nPOD program is expanding to recover additional organs relevant to T1D pathogenesis and complications from European countries (PanFin network).
Type 1 diabetes (T1D) is considered a disorder whose pathogenesis is autoimmune in origin, a notion drawn in large part from studies of human pancreata performed as far back as the 1960s. While studies of the genetics, epidemiology, and peripheral immunity in T1D have been subject to widespread analysis over the ensuing decades, efforts to understand the disorder through analysis of human pancreata have been far more limited. We have reviewed the published literature pertaining to the pathology of the human pancreas throughout all stages in the natural history of T1D. This effort uncovered a series of findings that challenge many dogmas ascribed to T1D and revealed data suggesting the marked heterogeneity in terms of its pathology. An improved understanding and appreciation for pancreatic pathology in T1D could lead to improved disease classification, an understanding of why the disorder occurs, and better therapies for disease prevention and management.
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