New study shows size and shape of encapsulation materials have an effect on islet cell survival
New York, NY, May 18, 2015 –Type 1 diabetes (T1D) researchers have known for nearly two decades that it is possible to make people living with T1D insulin independent through the use of islet transplants. One key barrier to broad use of this therapy is that islet transplants currently require recipients to use powerful immunosuppressant drugs that leave them vulnerable to other debilitating and life-threatening diseases, including cancer. These drugs are necessary to prevent the immune system from attacking and destroying the insulin-producing cells.
A collaborative team of researchers supported by JDRF and The Leona M. and Harry B. Helmsley Charitable Trust has been working hard at removing that particular barrier so that they can create islet implant therapies that will be applicable to most T1D patients. A new paper in the current issue of Nature Materials suggests they are making progress towards this goal. The researchers, led by Robert Langer, Ph.D., and Daniel Anderson, Sc.D., of the Massachusetts Institute of Technology (MIT), have been endeavoring to create encapsulation materials that will protect implanted islet cells from the immune system, yet allow the cells to sense changes in blood glucose and release the right amount of insulin and other blood-sugar controlling hormones at exactly the right time.
“One of the Langer and Anderson team’s most surprising findings is that the size and shape of the encapsulation material are just as important as the type of material when it comes to protecting and optimizing the life of implanted islet cells,” said JDRF Director of Discovery Research Albert Hwa, Ph.D. “This finding could be key to determining the best methods for creating highly effective, long-lasting encapsulated cell therapies for treating T1D.”
“We are pleased to support the important work of Drs. Langer and Anderson to identify the critical factors in a safe and effective encapsulation system, which has the potential to significantly impact the lives of people with type 1 diabetes, said Eliot Brenner, Ph.D., program director of the T1D Program at the Helmsley Charitable Trust.
A challenge to creating encapsulation technology is that the material used to house the islets must be robust enough to protect the cells from a direct attack by the immune system and biocompatible enough so that it doesn’t set off a localized immune reaction that can cause scarring around the implant and cut off oxygen to the cells, causing them to die shortly after implantation. Dr. Langer and Dr. Anderson’s team—which includes the paper’s lead co-authors Omid Veiseh, Ph.D., and Joshua Doloff, Ph.D., a former and current JDRF fellow, respectively—has been testing a large number of materials, including those made from seaweed and synthetic materials such as hydrogels and ceramics, in different sizes and shapes to determine which ones are most compatible with human tissue.
The research covered in the Nature Materials paper was based on two sets of experiments: one testing whether scarring occurred when just the encapsulation materials were implanted in small and large animal models and a second testing how long islets encapsulated in those materials functioned when they were implanted in a mouse model. In the first set of experiments, the team implanted 0.5 mm and 1.5 mm spherical-shaped encapsulation capsules made of seaweed hydrogel into mouse and primate models for 14 or 28 days. When the implants were removed, researchers found that scar tissue had developed around the smaller implants but not around the larger ones regardless of the length of time they were left in.
In the second experiment, researchers implanted 0.5 mm and 1.5 mm encapsulation capsules filled with insulin-producing islets from rats into a diabetic mouse model and found that the animals with the smaller implants maintained normal blood glucose levels for roughly 30 days while those with the larger ones maintained normal levels significantly longer and up to 180 days. When the capsules were retrieved, researchers again found scarring around the smaller implants, but not the larger ones, suggesting that the scarring had affected the islets’ viability and function.
“These are unexpected findings that came out of our effort to get to the bottom of what it will take to create a successful islet encapsulation system,” said Dr. Anderson. “We started out thinking it would be the materials, but now we know it’s a combination of factors.”
Drs. Langer and Anderson have received additional support from JDRF and the Helmsley Charitable to build on their recent research findings with new studies that will look to optimize the size and shape of encapsulation devices and use materials that are even more biocompatible than those used in previous experiments. They will also begin working with Harvard University stem cell researcher Douglas Melton, Ph.D., to develop an experimental encapsulated islet cell therapy implant. Completion of those experiments is a few years away.
About JDRF JDRF is the leading global organization focused on type 1 diabetes (T1D) research. JDRF’s goal is to progressively remove the impact of T1D from people’s lives until we achieve a world without T1D. JDRF collaborates with a wide spectrum of partners and is the only organization with the scientific resources, policy influence and a working plan to bring life-changing therapies from the lab to the community. As the largest charitable supporter of T1D research, JDRF has invested nearly $2B in research over the past 45 years and is sponsoring scientific research in 17 countries worldwide. For more information, please visit jdrf.org.
About the Helmsley Charitable Trust
The Leona M. and Harry B. Helmsley Charitable Trust aspires to improve lives by supporting exceptional nonprofits and other mission-aligned organizations in health, selected place-based initiatives, and education and human services. Since 2008, when the Trust began its active grant making, it has committed more than $1 billion. The Helmsley Type 1 Diabetes Program is the largest private foundation funder of T1D in the nation focused on understanding the disease, developing better treatments and improving care and access. For more information, visit www.helmsleytrust.org.