Curing Diabetes

Another significant step is being achieved by researchers at the DRI on the lengthy journey to bring islet cell transplantation closer to reality for individuals with type 1 diabetes.

Scientific research drives discovery into novel biological pathways that regulate normal bodily functions and can indicate alterations that may play a role in autoimmunity, cancer and other diseases. Understanding of the cells, molecules and genes involved in these pathways can lead to the development of drugs, cell therapies, devices and other technologies that might enable prevention, modification, or reversal of disease. But how do scientists take laboratory findings and translate them into people?

August 2022 – Dr. Giacomo Lanzoni is an Assistant Professor at the Diabetes Research Institute, University of Miami Miller School of Medicine. His research is focused on developing stem cell-based therapies for Type 1 Diabetes. In this disease, insulin-producing pancreatic islet beta cells are lost due to an autoimmune attack.

June 2022 – The Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine in Miami, Florida first began performing clinical islet transplantation in 1985. Since then, our center has blossomed into one of the largest independent centers worldwide, with 57 transplant recipients totaling 101 islet infusions since the year 2000.

May 2022 – Dr. Bayer’s lab focuses on Treg therapy and other autoimmune therapies. The main overarching goal of their current work is to better understand autoimmune-targeted treatments and how it can lead to diabetes reversal or late-stage development treatment. They focus on understanding the mechanisms by which the immune system provides immune regulation to maintain health and prevent disease.

April 2022 – Dr. Abdulreda’s DRIF funded project entitled “Mechanisms of Islet Transplant Immune Tolerance” aims to understand immune pathways that contribute to graft rejection or immune tolerance. Currently, islet transplantation requires continual immunosuppressive treatment to reduce the chance of islet graft rejection.

February 2022 – At the DRI, we have been studying Mesenchymal Stem Cells and their immunomodulatory properties for more than a decade. These cells can function as potent inhibitors of inflammation, can modulate immunity, and can stimulate Regulatory T cells (Tregs). Intense studies are ongoing at our Institute to use these cells to fend off autoimmunity in type 1 diabetes and to limit progression of diabetes complication.

DRI scientists developed a method allowing for the long-term culture of “pancreatic slices” to study the regeneration of the human pancreas in real time. The results, published Nature Communications, demonstrate for the first time that extended cultures of near-intact human pancreatic tissue retain the ability of the live organ to replenish insulin-producing beta cells. The use of this system as a model to study pancreatic regeneration could have important therapeutic implications for the treatment of diabetes.

Using continuous glucose monitoring (CGM), DRI scientists show that a small group of islet transplant recipients who were insulin independent for an average of 10 years have blood sugar levels that are similar to those without type 1 diabetes.

For the first time, DRI scientists engineer a stem cell line containing two ‘suicide genes’ that induce cell death in all but the desired insulin-producing cells. This double fail-safe approach, published in Stem Cell Reports, opens the door to advancing cell-replacement therapies for people living with type 1 diabetes.

Several scientific reports have suggested that high-dose omega-3 fatty acids and vitamin D may have a beneficial effect on autoimmune conditions, like type 1 diabetes. DRI researchers will formally test the effects of this intervention in children and adults newly diagnosed and in those with longer-standing T1D to evaluate any benefit on reducing inflammation, halting autoimmunity, and increasing insulin sensitivity and secretion.

DRI scientists confirm the existence of progenitor cells (pancreatic stem cells) within the large ducts of the human pancreas that can be stimulated to develop into glucose-responsive beta cells. The findings, published in Cell Reports, could pave the way to regenerating a person’s own insulin-producing cells in type 1 diabetes patients.

Currently, there is no good biomarker to detect whether the immune attack on the beta cells is underway. DRI researchers mapped out the biochemical changes that occur during type 1 diabetes onset, which is important not only for preventing the disease, but also for monitoring the recurrence of immune attack. This first-ever longitudinal study in experimental models was published in the Journal of Proteome Research.

DRI researchers report on the first trial participant to receive an islet transplant within a tissue-engineered scaffold, demonstrating that islets transplanted within this BioHub platform can successfully engraft and achieve insulin independence. The trial tests the omentum as an alternative transplant site. The one-year findings are published in the prestigious New England Journal of Medicine (NEJM).

The DRI develops and tests a bioengineered scaffold to house insulin-producing cells. This biological platform, which uses the recipient’s own plasma combined with thrombin, offers the opportunity to incorporate helper cells, nutrients, and local immune protection. These preclinical experiments are the basis for FDA submission for a Phase I/II clinical trial. The work is featured on the cover of the journal Diabetes.

DRI’s Dr. Allison Bayer and her team have developed a novel protocol demonstrating that adoptive Regulatory T cell (T reg) therapy can reverse the disease and reset autoimmunity in experimental models, achieving disease remission in 100 percent of the recipients. Importantly, the therapy was directed specifically at halting the destruction of the beta cells while the normal immune responses remained intact.

Researchers successfully convert non-insulin producing cells into insulin-producing cells using a single agent, BMP-7 (bone morphogenetic protein-7), which is already clinically approved by the FDA. Their published findings in Diabetes demonstrate for the first time that non-endocrine tissue can be reprogrammed to respond to blood glucose without the use of any genetic manipulation, representing a safer method to increase the supply of islets for transplant into people with T1D.

DRI researchers demonstrate that their unique cell coating process allows efficient encapsulation of islets without compromising viability and function of the cells. The team’s novel method for “shrink wrapping” each cell had been designed to specifically address what are considered to be the limitations of traditional cell encapsulation strategies. The results of their study earn the cover position in Proceedings of the National Academy of Sciences.

Scientists unveil their plan for the DRI BioHub, a bioengineered “mini organ” designed to mimic the native pancreas. The platform technology will contain thousands of insulin-producing cells that manage blood sugar levels in real time, plus other components that keep the cells healthy and viable long term. The DRI will focus on three primary areas: the development of a new transplant site; the development of a reliable supply of islets; and the ability to sustain the cells’ function without the need for harsh, systemic anti-rejection drugs.

Scientists from the Diabetes Research Institute (DRI) University of Miami Miller School of Medicine and DRI Federation center at Xiamen University (China) show that the use of mesenchymal stem cells (MSC) in kidney transplant recipients may replace a powerful anti-rejection drug. The results are published in the Journal of the American Medical Association (JAMA).

The DRI’s molecular biology team is the first to identify a disproportionately higher number of genes, called miR-7, in pancreatic islets compared to the non-islet tissue of the organ. These master regulatory genes are also found in fetal endocrine cells during development and play a central role in islet cell development, as well as in maintaining this endocrine function (as opposed to developing into other tissue). The findings are published in BMC Genomics.

Scientists show recurrence of type 1 diabetes may occur in patients after kidney-pancreas transplantation. Despite use of immunosuppression and continuous function of the kidney and exocrine portion of the transplanted pancreas, researchers identified the presence of autoimmune cells known to target insulin-producing cells. This study demonstrates the need to block the immune response to foreign tissue and prevent autoimmunity. The findings are published in Diabetes.

DRI researchers report on the success of an islet auto-transplant performed after severe trauma. Walter Reed Army Medical Center surgeons remove the 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 researchers develop novel method to monitor healthy islets in a living experimental model. For the first time, researchers can obtain real-time imaging of functioning islets transplanted in the anterior chamber of the eye. The clear “window” allows researchers to witness the islets in the same model over time as nerves and blood vessels develop and immune reactions occur. The work is featured on the cover of Nature Medicine.

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. The findings were published in the journal Stem Cells.

Scientists from the DRI’s islet physiology team discover that the internal structure of a 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. The findings were published Proceedings of the National Academy of Sciences (PNAS).

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 findings were published in the American Journal of Transplantation.

Scientists report for the first time that protein technology can be used to promote pancreatic cell differentiation. DRI’s Stem Cell and Molecular Biology teams use this technology to show how stem cells can be progressively educated along the pathway leading to functional beta cells. The findings, published in Diabetes, open a promising new avenue of research that might enable the development of more insulin-producing cells for transplant in the future.

Espousing its philosophy of global collaboration, the Diabetes Research Institute was asked to send members of its clinical cell transplant team to Shanghai’s First People’s Hospital to assist the Chinese team with both the islet isolation and transplantation efforts. Receiving telephone guidance from the DRI’s senior faculty, the DRI team in China was able to overcome every technical obstacle encountered, despite the formidable distance, technology, and language barriers.

Using a new combination of anti-rejection drugs and improved culture media for islets, the DRI’s cell transplant team performs a series of “islets alone” transplants in study participants with long-standing type 1 diabetes. The recipients are able to discontinue insulin therapy for more than a year following islet transplantation.

Using monthly injections of a monoclonal antibody, DRI is the first to show that transplanted islets reverse diabetes in pre-clinical models 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 subjects remain off insulin with glucose responsiveness for several months. The results are published in Proceedings of the National Academy of Sciences.

The DRI’s immunogenetics team 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.

Biopsies show intact, functioning human islet cells in the liver of a patient who was completely insulin independent for five years following an islet transplant.

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 donor pancreas. This technology leads to expansion of clinical trials in cell therapy for the treatment and cure of type 1 diabetes. The findings were published in the journal Diabetes.

DRI’s Rodolfo Alejandro, M.D., identifies a chemical that differentiates islets from non-islet tissue of the pancreas during the isolation process. This zinc-binding substance (dithizone) is absorbed only by islets, giving them a distinctive red color. This discovery enables researchers to optimize the cell separation process for improved clinical outcomes. It was also shown that the use of this substance does not interfere with islet function in vitro or in vivo. The findings were published in Transplantation.

Based upon results obtained in preclinical transplant models, DRI researchers begin the first human pilot clinical trial in patients with type 1 diabetes. The results of the pioneering study appeared in Advanced Models for the Therapy of Insulin-Dependent Diabetes.

DRI researchers conduct the first successful transplant of healthy islets into dogs with diabetes, restoring long-term natural insulin-production and normalizing blood sugar levels. Previously, these experiments were only successful in the rodent model. The findings were published in the journal Diabetes.

Using newly developed self-glucose monitoring and individualized algorithms for intensive insulin therapy, DRI researchers demonstrate that tight blood sugar control in women with type 1 diabetes during pregnancy can result in successful, full-term deliveries with normal birth weights. The study results were published in Diabetes Care.

Islet cells are successfully transplanted into rats with diabetes, restoring natural insulin production and normalizing blood sugar levels in laboratory animals. The results are published in the journal Diabetes.