DRC & Research News

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Improving Vascularization in Pancreatic Islet Transplants

One of the approaches scientists have been exploring for the treatment of type 1 diabetes is pancreatic islet cell transplants. By introducing these cells into the body, they are often able to maintain better glycemic control and support insulin production. However, there are many challenges that come with this type of treatment. It is essential to protect transplanted islet cells from immune system attack while also promoting sustainability. Cells tend to lose function over time and poor vascularization is often a contributing factor.

In a recent study, scientists have found a way to improve vascularization and therefore function of transplanted human pancreatic islets in diabetic mice. In addition to encapsulating islet cells, they also included human umbilical cord perivascular mesenchymal stromal cells or HUCPVCs. The HUCPVCs had a positive effect on graft function and suppressed T cell responses. In both immunocompetent and immunodeficient diabetic mice, glycemic control was maintained for up to 16 weeks when cells were transplanted via a kidney capsule, and for up to six weeks or seven weeks respectively when administered via a hepatic portal route. Furthermore, with the addition of HUCPVCs to the transplanted islet mass, rejection was delayed and the graft showed some proregenerative properties.

These findings may improve the future of human islet allotransplantation as a viable option for long-term treatment of type 1 diabetes. Scientists are constantly exploring ways to reduce rejection and the need for prolonged immunosuppression while maintaining better glycemic control. This study opens doors for more advanced research on the use of HUCPVCs in islet transplantation as well as related therapies.

Diabetes Research Connection is committed to supporting research for type 1 diabetes by providing early-career scientists with essential funding to keep projects moving forward. Learn more about current studies and how to donate to these efforts by visiting https://diabetesresearchconnection.org.

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Improved Beta Cell Function of Transplanted Islet Cells in T1D

One of the major challenges of using transplanted islet cells in the treatment of type 1 diabetes is cell death. Due to cellular stressors, poor oxygenation or vascularization, autoimmune response, and other factors, not all transplanted cells survive, and this can make treatment less effective. The body needs functional insulin-producing islet cells in order to effectively regulate blood sugar levels.

A recent study found that coculturing allogeneic islet beta cells with mesenchymal stromal cells (MSCs) may improve not only cell survival, but function as well. After donor cells are procured, they must be cultured and tested before being transplanted. This can generate significant cellular stress including hypoxia or low oxygenation, which can in turn lead to cell death. However, researchers found that MSCs support islet cells during this culture period by improving oxygenation and insulin secretion.

They also found that in response to these stressors, MSCs actually initiate mitochondria transfer to the islet beta cells.  This may improve mitochondrial ATP generation which plays an integral role in controlling insulin secretion. As a result, as glucose levels around the beta cells increased, so did their production and secretion of insulin.

Researchers experimented with this coculturing process with both mouse cells and human cells and found that human cells have a greater response and higher level of MSC-mediated mitochondria transfer that occurs. Though more extensive testing is necessary, these results show that MSCs may be an essential part of clinical islet transplantation and improved efficacy of beta cell function in treating individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how this study evolves moving forward and what it may mean for future therapeutic treatments for the disease. The DRC, though not involved in this study, provides critical funding for early career scientists pursuing novel, peer-reviewed research projects for type 1 diabetes. Learn more about current projects or how to support these efforts by visiting https://diabetesresearchconnection.org.

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Improved Protection for Transplanted Stem Cell-Derived Islets

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

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Improved Transplantation of Islet Organoids May Support Type 1 Diabetes Treatment

One approach to treating type 1 diabetes is transplanting insulin-producing beta cells into the body, or cells that can develop to perform this function. However, there are still many challenges in getting the body to accept these cells without extensive immunosuppression. Even still, the cells often have a limited survival rate.

In a recent study, scientists examined the potential of creating insulin-producing organoids to regulate blood sugar and treat type 1 diabetes. They combined dissociated islet cells (ICs) with human amniotic epithelial cells (hAECs) to form islet organoids, or mini pancreas-like organs. These organoids, which can contain multiple types of cells and cell functions, were transplanted into the portal vein because the area is easily accessible and has a low morbidity rate.

In similar approaches, researchers have been faced with cell death due to poor revascularization of the transplanted cells as well as inflammation. However, in this study, they found that by introducing hAECs, they were able to curb some of these effects. hAECs not only secrete proangiogenic growth factors, but anti-inflammatory growth factors as well including insulin-like growth factors and associated binding proteins. Furthermore, they produce high levels of hyaluronic acid which suppresses tumor growth factor β and stimulates VEGF-A production which supports improved revascularization. They also found that hAECs improved protection of IC-hAEC organoids against hypoxic stress thereby reducing risk of cell death.

Results showed that 96% of diabetic mice who received IC-hAEC organoid transplants achieved normoglycemia within one month. The median rate for this process to occur was 5.1 days. In addition, at one-month post-transplant, the mice showed similar glucose clearance as non-diabetic mice.

While this study has only been performed on mouse models so far, the goal is to achieve similar results in human trials. Additional research and testing are needed to determine if the process is translatable. This approach has the potential to improve management of type 1 diabetes and could lead to a possible cure for the disease if results are sustainable in the long-term.

Though not involved in this study, Diabetes Research Connection (DRC) supports advancements in type 1 diabetes research and treatment by providing critical funding to early career scientists. It is these types of studies that assist in transforming the future of diabetes care. Learn more and support these efforts by visiting http://diabetesresearchconnection.org.

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Protecting Pancreatic Islet Cells Following Transplantation for T1D

One of the challenges researchers have faced in developing long-term treatment options for type 1 diabetes (T1D) using allogeneic cells is that the body often rejects these cells. This means that patients would still need to take anti-rejection or immunosuppressant medications, which can be hard on the body and contribute to other issues. However, researchers may have found an option that protects cells while allowing them to control glucose levels.

In a new study, researchers encapsulated pancreatic islet cells with seven different alginate formulations and transplanted them into non-human primates. The goal was to maintain function of the cells without disruption by common challenges such as foreign-body response, pericapsular fibrotic overgrowth, or sedimentation of the microspheres. Of the seven alginates used, three showed transient islet graft function with decreased foreign-body response. One of the chemically modified microsphere formulations protected cells and glucose-response for four months without requiring immunosuppression.

This is a positive step toward correcting insulin deficiency using allogeneic cells. More research is necessary on the alginate formulations, and clinical trials have not yet been conducted in humans. The Diabetes Research Connection (DRC), though not involved in this trial, is interested to see where this study will lead and what it may mean for the future of T1D treatment options.

The DRC is committed to supporting T1D research and providing funding for early career scientists to carry out novel research projects. Learn more about current projects by visiting http://diabetesresearchconnection.org and consider donating to these efforts.

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Oxygen Supply May be Key in Supporting Islet Transplantation

One of the strategies scientists have focused on in the treatment of type 1 diabetes is transplanting healthy islet cells into the body to naturally produce insulin and manage blood glucose levels. These cells may be lab-generated or come from a donor. However, a major challenge has been conducting these transplants without reliance on immunosuppressants which can compromise overall patient health and complicate treatment.

In order to overcome this obstacle, researchers have created encapsulation devices to protect transplanted islet cells from attack by the body without using immunosuppressants. But with these devices, the lifespan of cells has been limited, in part due to poor oxygen supply. The devices often limit access to oxygen or restrict diffusion.

A new study has found that surrounding islet cells in an oxygen-permeable membrane and equipping the encapsulation device with an oxygen chamber can provide the necessary oxygen supply to keep cells functional and viable. Scientists experimented with varying levels of islet cell surface density and oxygen partial pressure (pO2).  The chamber allowed oxygen to be diffused throughout the highly concentrated alginate slab of islet cells.

The results showed that an average of 88% of islet cells maintained their viability and supported normoglycemic levels when tested in diabetic rats. Due to the continuous diffusion of oxygen, the chamber needs to be refilled daily through a subcutaneous port. Of the 137 rats in the trial, 66 remained normoglycemic for at least eight weeks. Some remained normoglycemic for up to 238 days, at which point the device was electively removed. Upon explanation, rats experienced hyperglycemia. When given intravenous glucose tolerance tests, results from rats with the implanted device were not significantly different than those of non-diabetic rats.

Researchers are currently exploring opportunities to decrease the size of the device while achieving greater islet density and continued viability. This study demonstrates how technology is advancing to create more options for treating and potentially curing type 1 diabetes with fewer complications and undesirable side effects.

Though not involved with this particular study, the Diabetes Research Connection is committed to supporting novel research for type 1 diabetes in an effort to prevent and cure the disease as well as reduce complications and improve quality of life for those living with type 1 diabetes. Visit us online at http://diabetesresearchconnection.org to learn more about current research projects and provide support for these initiatives.

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