The collaborative partnership of JDRF and The Leona M. and Harry B. Helmsley Charitable Trust has awarded a new grant in one of the most exciting and promising areas of type 1 diabetes (T1D) research. The $4.6-million grant, distributed over three years, will fund the beta cell encapsulation research of Camillo Ricordi, M.D., scientific director of the University of Miami Miller School of Medicine’s Diabetes Research Institute (DRI).
Beta cell encapsulation is a part of JDRF’s cure research portfolio that aims to make islet cell transplantation a therapeutic possibility for more people. While the procedure has been shown to improve quality of life, lessen insulin requirements, and reduce the frequency of hypoglycemic events in people with T1D, certain problems must still be addressed before the procedure can be made available to a wide number of recipients.
“Dr. Ricordi should be credited for working with a large number of international collaborators. He is looking to advance islet transplantation with the goal of making it more widely applicable to T1D individuals, and this is very much aligned with JDRF’s research strategy in this area,” says Albert J. Hwa, Ph.D., senior scientific program manager in beta cell therapies at JDRF. “He has also assembled a top-tier team at the DRI. The infrastructure there is well suited for conducting basic research and also translating the findings to large animal testing and eventually human clinical trials.”
One of the first challenges that Dr. Ricordi and his team are addressing is the poor survival rate of implanted islets. Currently, the most feasible implantation site for the islet cells is the liver, where hypoxia (oxygen deprivation) and inflammation often develop as a result. The researchers are investigating the omentum—a fold in the lining of the abdomen—for its easier access, larger space, and more hospitable environment for the islet cells.
Another significant problem of islet cell transplantation is a double threat from the transplant recipient’s immune system: first, the immune rejection that is a normal physiological response to transplanted foreign tissue; and second, the attack from the person’s T1D autoimmunity. Chronic immunosuppressive drugs are the conventional approach to this problem, but they come with additional health risks. Encapsulation—placing islets within a protective “capsule”—may resolve the issue.
Protecting implanted cells is crucial, but it must be done in such a way that the protection does not block the transplanted cells from receiving substances that are vital to their survival, or from doing their job. In other words, any protective material surrounding the cells must be able to let only certain things in, and certain things out. Dr. Ricordi’s team is developing a bioactive scaffold—a synthetic, protective structure that allows the cells to receive oxygen and other compounds from surrounding blood vessels and to perform the functions of healthy beta cells, releasing insulin to regulate blood-glucose levels. The cells will also receive an additional protective coating. Ultimately, the scaffold may preclude the need for immunosuppressive drugs.
“The scaffold technology has shown positive results in large animals, which gives us confidence in the probability of success,” says Dr. Hwa. “It is also a very flexible and modular platform that allows for additional engineering to further improve the cell transplant. It can accommodate many different encapsulation approaches. It can also be used to release compounds locally to benefit islet cells and to influence the immune system. The possible alterations are large and the approach can be continually improved.”
To read more about the science and promise of beta cell encapsulation, click here.