transplanted cells - Diabetes Research Connection

Diabetes Research News
May 28, 2020

Recapping Current Research Regarding Type 1 Diabetes Development and Cardiovascular Risks

Our bodies are formed from an innumerable number of cells and molecules. Both DNA and RNA play a role in determining cells’ function and purpose. At a conference of the National Congress of the Spanish Diabetes Society, researchers revealed new studies regarding the potential role of long non-coding RNAs (lncRNAs) in the development of type 1 diabetes, as well as the risk of cardiovascular problems in individuals with the disease.

A recent study found that lncRNA, which are use in transcriptional and post-transcriptional regulation of cells and are not translated into proteins, may be involved in the destruction of insulin-producing beta cells. There may be some forms of lncRNAs that affect inflammation and cell death, which are factors in the development of type 1 diabetes.

Dr. Izortze Santín Gómez, a professor at the University of the Basque Country and a researcher at the Biocruces Bizkaia Research Institute is studying the fundamental characteristics of the lncRNAs and how they may affect pancreatic beta cells on a genetic-molecular level. Once this is better understood, researchers could begin modifying the lncRNAs to create a targeted therapy that increases survival rate and viability of the pancreatic beta cells.

Another study that was presented at the conference involved cardiovascular risk for individuals with type 1 diabetes. Joseph Ribalta, a professor at the Rovira i Vigili University of Reus, found that “more than 30% of heart attacks occur in people with apparently normal LDL cholesterol.” High cholesterol is a key risk factor for heart attacks. His findings have revealed that individuals with T1D may be at greater risk because “LDL particles are more numerous and smaller, that their HDLs work less effectively and/or that there are some lipoproteins (remnants) that the body has trouble eliminating.”

Identifying these potential risk factors and knowing how to test for or treat them could help reduce hidden cardiovascular risk in individuals with T1D. For instance, focusing on triglycerides rather than cholesterol may be beneficial for patients who meet certain criteria.

There is a lot of interesting work coming out of laboratories and universities around the world regarding type 1 diabetes. Researchers are constantly improving and refining their understanding of the disease and possible ways to prevent, treat, or cure it. Diabetes Research Connection (DRC) is committed to contributing to this wealth of knowledge by providing critical funding to early-career scientists pursuing novel research studies focused on type 1 diabetes. Click to learn more about current projects and provide support.

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Diabetes Research News
May 26, 2020

Increasing Cell Protection Against Immune System Attacks

One of the challenges researchers have faced with using cell therapy to treat type 1 diabetes is that the body’s immune system may still attack and destroy transplanted cells. This process may be slightly delayed depending on the approach used, but it often still occurs. That means that patients may still need to rely on immune suppression medications in conjunction with cell therapy. However, immunosuppression can increase risk of infection or other complications.

A recent study found that targeting highly durable cells that have the ability to escape immune attacks and survive may be key in developing a more effective treatment for type 1 diabetes. Dr. Judith Agudo has identified stem cells with this “immune privilege” and is working to determine exactly what contributes to this level of protection and how to replicate it with beta cells. Dr. Agudo is an assistant professor in the department of immunology at Harvard Medical School and in the department of cancer immunology and virology at the Dana-Farber Cancer Institute.

If scientists can engineer insulin-producing beta cells that have the ability to avoid attacks from the immune system while still performing their intended functions, this could be a huge step forward in potentially treating type 1 diabetes. The beta cells would be able to stimulate insulin production without requiring the patient to take immune suppression medications, meaning their immune system could continue to function as normal and fend off infection.

Once Dr. Agudo is able to develop these durable beta cells, they will be tested in animal models, followed by humans a few years later. It is important to conduct thorough testing to ensure this method is both safe and effective. If it is, the goal would be to eventually make it available to anyone who requires the use of insulin.

Diabetes Research Connection (DRC) is excited to see how this study evolves and what it could mean for the future of diabetes treatment. While not involved in this study, the DRC plays an integral role in providing critical funding for early career scientists focused on research for type 1 diabetes. Scientists continue to advance understanding of the disease and potential approaches to improve diagnosis, treatment, management, and quality of life for individuals living with type 1 diabetes. Click to learn more about current projects and provide support.

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Diabetes Research News
April 16, 2020

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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Diabetes Research News
April 14, 2020

Advances in Therapeutic Treatment for Type 1 Diabetes without Immune Suppression

One approach that researchers have been exploring to treat type 1 diabetes is cell therapy. By introducing new insulin-producing beta cells or other types of cells, scientists strive to support the body in once again producing its own insulin. A common challenge with this technique is that it often has limited results as the body once again attacks the cells, or they slowly lose function on their own. In addition, cell therapy typically requires immune suppression which can put individuals at risk for other complications.

However, in a recent study, researchers tested a new method of transplanting therapeutic cells by using a retrievable device with a silicone reservoir. The cells are further protected by a porous polymeric membrane that allows macrophages to enter the device without destroying the transplanted cells, or that prevents them from entering at all.

When tested in immunocompetent mice, the device supported normoglycemia for more than 75 days without the need for immunosuppression. The transplanted cells were able to effectively produce erythropoietin, which in turn improves oxygen supply to the body, and also generates insulin to manage blood sugar levels.

This is a notable step forward in improving cell therapy for the treatment of type 1 diabetes. More research and testing are required to determine how this process translates into human models. Researchers have been trying to limit or eliminate the need for immune suppression while transplanting healthy pancreatic, islet, and stem cells into the body to control blood glucose levels.

Dan Anderson, Ph.D., a member of the Diabetes Research Connection (DRC) Scientific Review Committee, is the senior author of the article published regarding these findings. DRC is excited to see where these advances may lead and what it could mean for the future of cell transplantation techniques and cell therapy for type 1 diabetes. The organization provides critical funding for a wide range of projects related to improving diagnosis, treatment, and prevention of the disease. Learn more about current studies and how to support these efforts by visiting https://diabetesresearchconnection.org.

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Diabetes Research News
February 19, 2020

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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Diabetes Research News
November 4, 2019

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. Click to learn more about current projects and provide support.

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