immunosuppression - Diabetes Research Connection

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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Diabetes Research News
October 14, 2019

Antibody-Drug Conjugate May Help Reduce Allograft Rejection.

Cell transplantation has been an area of focus in developing treatment for type 1 diabetes. Many studies have examined both autologous and allogeneic transplants and the benefits and risks they provide. A major challenge continues to be rejection and the body’s destruction of these cells, whether initially derived from its own cells or not.

However, a recent study found that an anti-CD103 antibody-drug conjugate (M290-MC-MMAF) may reduce pancreatic islet allograft rejection in mice. This drug decreased the amount of CD103⁺CD8⁺ effector T cells while at the same time increasing the amount of CD4⁺CD25⁺ regulatory T cells. This balance led to improved survival rate of the allograft and supported immunosuppression without causing systemic toxicity. When CD103⁺CD8⁺ levels were increased, allograft rejection quickly followed.

While this study has only been conducted in mouse models, it shows potential for pancreatic islet allografts in treating type 1 diabetes. Further research is necessary to determine how this process translates to human cells. M290-MC-MMAF could eventually be used as a therapeutic intervention to reduce risk of allograft rejection in humans.

Diabetes Research Connection (DRC), though not involved in this study, stays abreast of the latest discoveries in the field and supports early career scientists in pursuing novel, peer-reviewed research projects related to type 1 diabetes. Scientists receive funding that is critical to conducting research and improving the diagnosis, treatment, and management of the disease and one day finding a cure. To learn more about current projects and how to support these efforts, visit http://diabetesresearchconnection.org.

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