Nearly 40 Years of Cure-Focused Diabetes Research
The DRI has received approval from the Food and Drug Administration (FDA) to proceed with with a Phase I/II clinical trial that will test the omentum as a possible transplant site for a DRI BioHub. In this pilot trial, researchers will transplant insulin-producing islet cells within a "biodegradable scaffold," one of the approaches considered for a BioHub platform.
DRI scientists unveil the DRI BioHub, a bioengineered mini organ that mimics the native pancreas, containing thousands of insulin-producing and other cells that sense blood glucose and release the precise insulin needed in real time. Components of the DRI BioHub are in different stages of testing, with first stage clinical pilot trials planned within the year.
Scientists from the Diabetes Research Institute (DRI) University of Miami Miller School of Medicine and DRI Federation center at Xiamen University (China) show the use of mesenchymal stem cells (MSC) in kidney transplant recipients may replace a powerful anti-rejection drug. The results are published in the March 21 issue of the Journal of the American Medical Association (JAMA).
DRI’s Tissue Engineering team develops a revolutionary oxygen-generating biomaterial to enhance islet transplant survival. Their report is publishedin Proceedings of the National Academy of Science (PNAS).
The American College of Physicians recognizes the Diabetes Research Institute with the prestigious Samuel Eichold II Memorial Award for Contributions in Diabetes, given for important innovations in health care delivery for diabetic patients, which improve clinical or economic outcomes.
The DRI’s Molecular Biology group identifies the expression profile of microRNAs during human pancreatic development. A Bioinformatics analysis suggests an intertwined network of master regulatory genes collaborating with each other. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development. The results are published in BMC Genomics.
DRI scientists show that recurrence of type 1 diabetes may occur in patients following combined kidney-pancreas transplantation, despite chronic immunosuppression that prevents rejection. Researchers identified autoimmune cells against target insulin-producing beta cells, and are monitoring more patients to better understand how to treat this underappreciated cause of graft loss. The findings are published in the journal, Diabetes.
DRI researchers report on the success of an islet auto-transplant performed after severe trauma. Walter Reed Army Medical Center surgeons remove the badly damaged pancreas from a soldier wounded in the Middle East. The tissue is sent to DRI where islets are isolated and sent back for transplant into the same patient preventing diabetes. The findings, published in the New England Journal of Medicine, indicate that islet isolation and auto-transplant in cases of severe abdominal trauma can be performed using a remote processing center.
DRI’s Drug Discovery Program demonstrates that small molecules can effectively block a specific pathway involved in the immune rejection of islets. The findings published in the Journal of Molecular Recognition and in the Journal of Molecular Medicine, open the door to safer and more effective therapies for cell replacement.
DRI researchers develop a novel method to monitor healthy islets in a living organism. For the first time, researchers can obtain real-time imaging of functioning islets transplanted in the anterior chamber of the eye and observe nerve and vascular development, immune reaction among other vital mechanisms. The work is published in Nature Medicine and featured on the journal’s cover.
The DRI’s Molecular Biology program identifies master regulatory molecules specific to insulin-producing islets. Known as microRNA’s (miRNA), the team is first to discover miRNA-7 as key to beta cell development. The research is published in Biochemical and Biophysical Research Communications.
DRI’s Islet Physiology team identifies a critical mechanism involved in the release of glucagon from healthy islets. The findings, published in Cell Metabolism, and featured on the cover of the prestigious journal, show that the neurotransmitter, glutamate is a positive autocrine signal and key to the release of glucagon from the alpha cells within islets. It is this component of the regulatory mechanism that prevents hypoglycemia.
Scientists at the DRI design and test a new cell culture device that closely mimics the natural oxygen environment, demonstrating a dramatic increase in beta cell development from an embryonic mouse pancreas.
Scientists from the DRI’s Signal Transduction Laboratory discover that the internal structure of the human islet cell is dramatically different from the more often studied rodent islet – a striking finding that argues for the importance of studying human islets if medical research is to benefit people living with diabetes.
A Diabetes Research Institute study shows type 1 diabetes patients’ quality of life and sense of well-being improve following islet transplantation despite having to take harsh anti-rejection drugs.
The DRI's Human Immunology team identifies a group of antigen-presenting cells responsible for the production of insulin in the thymus and peripheral blood. Scientists believe these cells play a key role in establishing and maintaining self-tolerance to insulin itself.
DRI investigators publish a method for obtaining more islets from a single donor organ. The results, which appear as the cover story of American Journal of Transplantation, show how DRI’s Human Cell Processing team can now obtain 27% more healthy human islets using the rescue gradient purification (RGP) method.
Scientists report that, for the first time, protein technology can be used to promote pancreatic cell differentiation. DRI Stem Cell and Molecular Biology teams use this unique technology to show how stem cells can be progressively educated along the pathway leading to functional beta cells. The findings are published in Diabetes, and open a promising new avenue of research that might enable the development of more insulin-producing islet cells for transplantation in the future.
DRI scientists develop a new culture media to preserve isolated islets for transplantation, allowing islets to “rest” and improve their function over a 2-3 day period. Previously, the immediate transplant of isolated islets was required, however, this new solution provides adequate time for transplant recipients to arrive at the DRI. Recipients travel from Georgia, New Jersey, Oregon, and as far away as Alaska to participate in DRI clinical trials. This DRI discovery enables the first State-to-State islet transplant with DRI providing the cells for Texas’ first successful islet cell transplant.
Immunogenetics laboratory at the DRI, headed by Alberto Pugliese, M.D., identifies the cells that express insulin in the thymus and other organs of the immune system. The findings, published in the Journal of Clinical Investigation, describe a novel subset of cells that make small amounts of insulin and other islet molecules termed “self antigen presenting cells.” These cells appear to play a crucial role in the regulation of immunological tolerance to islet molecules. Further studies will address clinical application for promoting and restoring self-tolerance to help prevent diabetes and the potential recurrence of diabetes after islet transplantation.
Using monthly injections of a new monoclonal antibody, the DRI's pre-clinical research team, led by Norma S. Kenyon, Ph.D., is the first to show that transplanted islet cells reverse diabetes in monkeys without the need for any other anti-rejection drug. The recipients remain insulin independent for over one year post-transplant and emerging rejection episodes can be reversed using this antibody. Even after discontinuation of the antibody, many animals remain off insulin for several months.
DRI scientist Alberto Pugliese, M.D. publishes new findings related to insulin production in the thymus and its role in the development of type 1 diabetes. The Nature Genetics paper describes how this type of insulin might play a key role in the immune system’s ability to recognize insulin molecules as “self”. Scientists believe that the amount of thymic insulin might determine either susceptibility to or protection from diabetes.
A multi-center comparison of islet cell transplantation and current diabetes management practices shows that successful or even partially successful islet transplants can more effectively control blood glucose (and do so without hypoglycemic episodes) than either conventional or intensive insulin therapy.
Biopsies show intact, functioning islet cells in the liver of a patient who was completely insulin independent for five years following an islet transplant.
Experiments with islet transplants prove that it is possible to reverse diabetes and achieve complete insulin independence in pre-clinical models without the use of continuous immunosuppression.
Nine patients receive islet cells in conjunction with their multi-organ transplants. This study, published in The Lancet, demonstrates that islets can produce insulin independence in patients who had previously been pancreatectomized.
Camillo Ricordi, M.D., develops an automated method for isolating large numbers of islets from a single pancreas. This technology enables scientists to consider a wider application of islet cell transplantation as a potential cure for diabetes.
DRI investigators use a zinc-binding substance (dithizone) to stain and better visualize islet during the isolation process. They also show that this new method does not interfere with islet function in vitro or in vivo.
DRI performs islet transplant in a patient already requiring immunosuppression for a transplanted kidney. The procedure results in a 75% reduction of the patient’s insulin requirement for almost one year.
The first successful transplant of healthy islets into dog with diabetes is performed, effectively curing them of their diabetes.
Using self-glucose monitoring and intensive insulin therapy, DRI researchers develop a successful treatment for pregnant women with diabetes. The risk of miscarriage drops markedly for these future mothers, and their chances of giving birth to healthy children rise significantly.
Islet cells are successfully transplanted into rats with diabetes, producing a cure for diabetes in laboratory animals. The results are published in the journal Diabetes.