Gordon Weir, M.D., Co-Head of the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center, has teamed up with MIT researchers Robert Langer, Ph.D., Institute Professor, and Daniel Anderson, Ph.D., Associate Professor, to move the type 1 diabetes field one step closer to a cure. The four-year old collaboration tackles the problem of protecting transplanted beta cells (the islet cells that secrete insulin) from continued autoimmune attack.
The beta cells of people with type 1 diabetes are almost entirely destroyed by the immune system, which means these individuals produce little to no insulin. Attempts to replace the failing beta cells are met with the same autoimmunity that caused the problem in the first place, with the added difficulty of transplant rejection (when another part of the immune system attacks the donor cells).
A technique called encapsulation seemed like a way around this problem. Take an islet cell, wrap it in protective material, and it will be safe from the autoimmune onslaught.
Coating islets has proved fairly easy; they can be coated with a seaweed-derived gel called alginate. The islet/alginate liquid mixture falls as droplets into a salt bath which binds strands of alginate together into a tightly woven mesh around the islet. The weave is loose enough that insulin can get out and the nutrients the cell needs to survive can get in, but tight enough that the autoimmune T-cells aiming to destroy the beta cells can’t get through.
While encapsulation prevents T-cells from getting to the islets, there may still be problems because the immune system can sometimes recognize the capsules as a foreign invader. This perceived threat is met by layering scar tissue around the capsules, thus preventing oxygen and other nutrients from getting to the beta cells.
Researchers realized they needed to somehow trick the immune system into thinking the capsules were part of the body’s biology. So the JDRF approached Dr. Langer, an expert in biomaterials, about creating a new type of alginate that would fix the problem.
The labs of Dr. Langer and Dr. Anderson started modifying the existing alginate to see what properties they could add that would make it more invisible to the immune system. They brought Dr. Weir and his Joslin lab on board to consult on the process and the biology.
The MIT labs use robots to make hundreds of new versions of the alginate with different potentially biocompatible properties.
They’ve been adding some extra features, as well. While the alginate is more biocompatible than before, it’s not a perfect match to the transplant recipient, so the capsules still stimulate some immune response. The MIT labs embed into the capsule an anti-inflammation drug that is slowly released throughout the first seven days of the transplant—the post-implant period with the most active immune response.
But some anti-inflammatory drugs may interfere with the secretion of insulin. To avoid this step backwards, the scientists are working to create two layers within the capsule. The first houses the insulin-secreting beta cells. The second releases the anti-inflammatory drugs, so the drugs and beta cells never come in contact.
When the researchers come up with a combination of properties that could work, they encapsulate islets in the new material and test it in a mouse model of type 1 diabetes.
This collaboration among MIT, Joslin, and JDRF has already yielded positive results in rodents. The next step is to try the successful alginates in larger animals to see if the capsules can withstand more robust immune systems.
While encapsulated islets wouldn’t be a complete cure—that would require something to also halt the body’s autoimmunity to beta cells—it would allow beta cells to act naturally, freeing people with type 1 diabetes from multiple daily injections, untethering them from pumps, and ending glucose testing.