Network for Pancreatic Organ Donors with Diabetes

Network for Pancreatic Organ Donors with Diabetes
Founded 2007
Focus Recovering donated tissues from organ donors with type 1 diabetes and sharing them with approved researchers seeking to prevent, reverse, and cure the disease.[1]
Origins The criticial need to understand the human pancreas
Area served
International
Method Collaborative Research
Key people
 Mark Atkinson, Alberto Pugliese
Endowment JDRF
Website www.jdrfnpod.org

The Network for Pancreatic Organ donors with Diabetes (nPOD), is a collaborative type 1 diabetes research project funded by JDRF (formerly known as the Juvenile Diabetes Research Foundation). nPOD supports scientific investigators by providing, without cost, rare and difficult to obtain tissues beneficial to their research. nPOD currently supports more than 100 type 1 diabetes-related scientific studies at institutions around the world, fostering an unparalleled environment of data sharing and collaboration. Our hope is that nPOD will prove a useful resource to the community of researchers dedicated to finding a cure for type 1 diabetes.[2]

History and Mission

Type 1 diabetes (T1D) results from an autoimmune response against the insulin producing beta cells of the pancreas.

An islet with insulitis associated with type 1 diabetes.

This destruction of beta cells causes patients to develop a lifelong dependence on insulin replacement therapy. Unfortunately, insulin injections are often insufficient for preventing many severe complications including heart disease, kidney failure, and blindness, among others. The disease process that leads to the development of T1D has been under investigation for more than 100 years. Several of the major players have been identified, but many key mechanisms of disease development remain undiscovered.[3]

The majority of studies investigating type 1 diabetes have been performed in rodents due to the lack of availability of human tissues. While these studies have allowed us to identify potential causes for T1D and have directed many researchers in the development of their methods, key biological differences between rodents and humans prevent their use to uncover the specifics of disease progression.[4] nPOD grew out of a vision to bridge this gap of understanding by creating a biobank to collect and distribute diabetes-associated human tissues to researchers.

JDRF recognized this reality and took on the vision to create a biobank of human tissue for type 1 diabetes research, despite the notion of the time that it was an impossible feat. JDRF asked Mark Atkinson, PhD, at the University of Florida to drive this initiative. He agreed and gathered a team. Together they took on the challenge of creating nPOD.[5] Since 2007, nPOD has grown from supporting seven researchers to more than 100 projects. Several members have been added to the administrative, processing, and data management teams to handle the success of the project that was believed to be impossible.

The goals of nPOD are twofold:[6]
  • First, to maintain a network of procuring and characterizing pancreas and related tissues (spleen, duodenum, lymph nodes, pancreatic lymph nodes, and peripheral blood) from cadaveric organ donors with type 1 diabetes as well as those who are positive for islet autoantibodies but have yet to develop T1D.
  • Second, to promote collaboration through investigator utilization of these tissues and data sharing in an effort to address key immunological, histological, viral, and metabolic questions related to the development of type 1 diabetes.

Organization and Partnerships

Recovery Partners

nPOD partners with Organ Procurement Organizations (OPOs) and tissue banks to identify deceased organ donors who wish to donate to research and have been diagnosed with type 1 diabetes or are pre-clinical (identified by autoantibody testing). When these donations are not suitable for transplant, the pancreas and related tissues are recovered by the OPO and sent to nPOD for processing, storage, and pathological characterization.

Screening

Biological markers associated with type 1 diabetes have been identified and are used by physicians and researchers to determine the predisposition and/or disease progression of a donor. Of these markers, nPOD tests for C-Peptide, autoantibodies, and HLA. C-Peptide is an indication of insulin secretion and is measured for all donors. There are at least 4 major autoantibodies associated with the predisposition and progression of T1D: GAD-65, IA-2, mIAA, and ZnT8. A positive correlation has been identified that shows a person who is positive for multiple autoantibodies is more likely to develop diabetes.[7] In order to identify donors who are predisposed or are in the processing of developing diabetes but have not been clinically diagnosed, nPOD has set up a relationship with screening labs to test for these autoantibodies in conjunction with the serologies performed for the OPO. Following processing, serum from all nPOD donors is sent to the Autoantibody Core at the University of Colorado to be tested for autoantibodies. Autoantibody positive non-diabetic donors are rare, but they provide unparalleled insight to the mechanism of disease progression. The genes that have shown the strongest association with T1D risk and protection belong the HLA category.[8] All donors are typed for the following HLA alleles: A, B, DRB1, and DQB1.

Case Processing

The processing team, also known as the Organ Processing and Pathology Core (OPPC), is responsible for sample processing, inventory, and distribution, as well as the pathological evaluation of tissues that are available in the online pathology database. This database allows researchers to view samples and their associated morphology, diagnosis, and donor demographics. In addition to maintaining this database, the OPPC team works with investigators to choose the cases that best fit their experiment needs and they also perform quality control studies to ensure that the best tissue processing methods are being practiced.[9]

Administrative Core

The Administrative Core coordinates relationships with OPOs and screening labs, investigator relations, special projects, and oversees day-to-day operations.[10] Together with the OPPC and Administrative Core, the Data Management Core, based at City of Hope in Duarte, California, works to maintain all data related aspects of nPOD. Currently, nPOD is in the beta testing stages of a new interactive database that allows researchers to view de-identified donor information, review the pathology database, peruse the sample inventory, and upload their data. This new program provides an unparalleled platform for data sharing and collaboration.[11]

Investigators and Research

Projects

nPOD currently supports more than 100 type 1 diabetes research projects. nPOD and all associated studies are approved by the Institutional Review Board (IRB) at their respective institutions. Studies using nPOD tissues span several categories including beta cell regeneration, diabetes-associated metabolic and developmental mechanisms, immunology, pathology, and etiology of type 1 diabetes.[12] Investigators must go through a rigorous approval process to obtain the rare and precious tissues donated to nPOD. This process begins with an application that details their study, methods, justification of tissue requested, IRB approval, and a confidentiality agreement. The Tissue Prioritization Committee evaluates all applications for scientific merit and originality. These criteria ensure the most effective use of tissue and prevent study duplication. Once approved, investigators are assisted by the investigator relations administrator and the OPPC director, for study coordination and legalities as well as determination of the most appropriate samples for their studies.

DataShare

A new platform for investigators to work together called DataShare has been developed to enhance nPOD’s collaborative mission. This database allows nPOD researchers to search the sample inventory, review all histopathology and de-identified donor data, and upload their data for sharing.

Annual Meeting

Each year, the nPOD investigators gather for a few days to present and discuss their recent data. This crucial conference allows investigators spanning a wide range of specialties from around the world to share ideas. Working sessions take place in which groups of investigators with different expertise meet to address specific questions related to diabetes. These meetings often result in new approaches for understanding the disease and the development of new collaborations.[13]

Initiatives

nPOD-Virus

nPOD-Virus (nPOD-V) is a working group made up of nPOD investigators who are seeking to identify the role of viruses in type 1 diabetes through a collaborative study on nPOD samples. Several previous studies have implicated the role of enterovirus infection in islet autoimmunity and diabetes, but these studies had several limitations and the details of the proposed effects of virus have yet to be uncovered. The nPOD-V collaboration has been organized into several specific task teams and uses real-time data sharing. The structure of this group has the potential to be replicated for the investigation of other key mechanisms involved in diabetes.[14]

nPOD-Transplant

nPOD-Transplant (nPOD-Tx) is an initiative funded by the JDRF and based at the University of Miami that aims to understand the recurrence of type 1 diabetes in patients who have received a pancreas transplant. By studying these tissues, investigators will achieve a more in-depth understanding of the long-term persistence of islet autoimmunity and the regenerative capability of the pancreas. Due to the post-transplant immunosuppression, these tissues may potentially address critical questions about the development of type 1 diabetes and the means for a cure.[15]

nPOD-Europe

nPOD-Europe (nPOD-E) is an extension of the nPOD program into Europe with the goal of expanding organ collection and distribution through the creation of qualified sites in European countries. This project is in collaboration with PEVNET, a multi-center organ recovery initiative in Europe.[16]

Ethical Considerations

nPOD has been approved by the local IRB at the University of Florida and is compliant with all state and federal regulations. The Administrative and Processing Cores routinely undergo in-depth evaluations to ensure regulatory standards are met. Additionally, all studies associated with nPOD are required to be approved by the IRB that oversees their respective institutions.[17]

Diabetes Resources

To learn more about diabetes and research: JDRF American Diabetes Association University of Florida Diabetes Center of Excellence University of Miami Diabetes Research Institute

Organ Donation

Information about organ donation

References

  1. ↑ http://www.jdrfnpod.org
  2. ↑
  3. ↑ http://www.jdrfnpod.org/mission.php
  4. ↑ Roep, Bart. “Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes”. Nat Rev Immunol. 2004;4(12):989-97
  5. ↑ Dinsmoor, Robert S. "The Little nPOD That Could." JDRF Countdown Spring 2010: 12-14. Print.
  6. ↑ http://www.jdrfnpod.org/mission.php
  7. ↑ Atkinson, Mark. “Type 1 diabetes”. The Lancet. July 26, 2013.
  8. ↑ Eisenbarth, George. “Prevention of type 1A diabetes mellitus. Endocr Pract. 2012;18(5):745-9.
  9. ↑ http://www.jdrfnpod.org/how-we-work.php#oppc
  10. ↑ http://www.jdrfnpod.org/how-we-work.php#admin
  11. ↑ http://www.jdrfnpod.org/online-pathology.php
  12. ↑ http://www.jdrfnpod.org/our-investigators.php
  13. ↑ http://www.jdrfnpod.org/2013-annual-meeting.php
  14. ↑ http://www.jdrfnpod.org/news-and-events.php
  15. ↑ http://www.jdrfnpod.org/transplant.php
  16. ↑ http://www.jdrfnpod.org/Europe.php
  17. ↑ http://www.jdrfnpod.org/how-we-work.php
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