Network for Pancreatic Organ Donors with Diabetes (nPOD): developing a tissue biobank for type 1 diabetes

Abstract

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).

The diagnosis of insulitis in human type 1 diabetes

“…As discussed above, it was also recognised that different studies dealing with histopathological changes in the type 1 diabetic pancreas have used different thresholds to define insulitis. These thresholds range from two to 15 CD3 + or CD45 + cells adjacent to or infiltrating the islet [6,[9][10][11][12][13][14]. However, recent observations in a cohort of 363 non-diabetic donor pancreases indicate that the level of background infiltration in the pancreatic parenchyma is highly variable and dependent on the clinical conditions surrounding organ retrieval, with the highest levels of infiltration observed in patients with a prolonged duration of life support [15].…”

Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora’s box

“…Indeed, if anything, this outcome should bolster alternative approaches to evaluate the inner workings of the pancreas, including and especially pancreatic imaging via NMR or PET [10]. These efforts also provide support, albeit indirect, for initiatives designed to collect whole pancreases from organ donors, such as PanFin and the Network for Pancreatic Organ Donors with Diabetes (nPOD) (www.jdrfnpod.org) [11,12]. These efforts not only evaluate cases with type 1 diabetes but, in addition, presumed 'prediabetic' pancreases obtained from non-diabetic individuals who possess anti-islet cell autoantibodies.…”

Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

“…Insulitis is present at weaning and the insulitic infiltrates are heavy. In comparison, islet inflammation appears to be a rare event in man [20][21][22][23][24][25][26][27]. However, based on genetic homogeneity throughout the NOD colonies held worldwide, the mouse strain represents a single individual with diabetes or a family with a given genetic susceptibility.…”

“…Further, efforts such as the Network for Pancreatic Organ Donors with Diabetes (nPOD) [20,21] and those in Europe [22][23][24][25][26][27] are highlighting differences between the insulitic lesion comparing individuals with T1D and autoantibody-positive organ donors. This high level of heterogeneity in disease, even amongst twins or the NOD mouse, should refocus the attention on the genetic causes.…”