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

Alberto Pugliese, Mingder Yang, Irina Kusmarteva, Tiffany Heiple, Francesco Vendrame, Clive Wasserfall, Patrick Rowe, Jayne M Moraski, Suzanne Ball, Les Jebson, Desmond A Schatz, Roberto Gianani, George W Burke, Concepcion Nierras, Teo Staeva, John S Kaddis, Martha Campbell-Thompson, Mark A Atkinson, Alberto Pugliese, Mingder Yang, Irina Kusmarteva, Tiffany Heiple, Francesco Vendrame, Clive Wasserfall, Patrick Rowe, Jayne M Moraski, Suzanne Ball, Les Jebson, Desmond A Schatz, Roberto Gianani, George W Burke, Concepcion Nierras, Teo Staeva, John S Kaddis, Martha Campbell-Thompson, Mark A Atkinson

Abstract

nPOD actively promotes a multidisciplinary and unbiased approach toward a better understanding of T1D and identify novel therapeutic targets, through its focus on the study of human samples. Unique to this effort is the coordination of collaborative efforts and real-time data sharing. Studies supported by nPOD are providing direct evidence that human T1D isa complex and heterogeneous disease, in which a multitude of pathogenic factors may be operational and may contribute to the onset of the disease. Importantly, the concept that beta cell destruction is almost completed and that the autoimmune process is almost extinguished soon after diagnosis is being challenged. nPOD investigators are exploring the hypothesis that beta cell dysfunction may also be a significant cause of hyperglycemia, at least around the time of diagnosis, and are uncovering novel molecules and pathways that are linked to the pathogenesis and etiology of human T1D. The validation of therapeutic targets is also a key component of this effort, with recent and future findings providing new strategic direction for clinical trials.

Keywords: TID; beta cell; organ donation; pancreas; virus.

Figures

Figure 1
Figure 1
The Network for Pancreatic Organ Donors with Diabetes (nPOD) operational model. The diagram illustrates the current strategy used to obtain organ donors for diabetes research described in the main text.
Figure 2
Figure 2
Pancreas pathology from Network for Pancreatic Organ Donors with Diabetes (nPOD) T1D donor 6195. Pancreas serial sections were stained with double immunohistochemistry (IHC) stains (CD3 and glucagon, Ki67 and insulin, brown and red, respectively). Pseudoatrophic islets (glucagon-positive cells only) are located adjacent to an insulin-positive islet in this section. Insulitis is detected by numerous CD3+ T cells adjacent to and infiltrating two islets (arrows). The donor was a 19-year-old Caucasian male with 5 years T1D duration.
Figure 3
Figure 3
Pancreas pathology from T1D donor nPOD 6046. Pancreas section stained for insulin (dark) by immunohistochemistry and counterstained with hematoxylin. The donor was an 18-year-old Caucasian female, who had developed T1D 8 years prior. A significant numbers of islets stain well for insulin, indicating the presence of beta cells, at least in some lobules, despite 8 years of disease duration.

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