Scientists searching for Type 1 diabetes cures have long been interested in transplanting functioning pancreatic islet cells into patients, but the danger of immune system rejection has been an obstacle. A team from from Georgia Tech, the University of Louisville and the University of Michigan, however, transplanted islets into mouse models of diabetes, along with a hydrogel that trains immune cells to accept the transplants.
The combination staved off rejection in the mice. If the findings translate to humans, the procedure could treat diabetes without the need for long-term immunosuppressive drugs.
The researchers created polymer hydrogel particles that presented Fas ligand (FasL), a protein that "educates" immune cells known as T-effector cells to accept islets without rejection. They then mixed the hydrogel particles with pancreatic islets before transplantation.
The cells were delivered to the animals' kidneys and abdominal fat pads. The mice did not reject the graft for at least 200 days. The study appears in the journal Nature Materials.
"We have been able to demonstrate that we can create a biomaterial that interrupts the body's desire to reject the transplant, while not requiring the recipient to remain on continuous standard immunosuppression," said Haval Shirwan of the University of Louisville, in a statement. "We anticipate that further study will demonstrate potential use for many transplant types, including bone marrow and solid organs."
A permanent cure for Type 1 diabetes—one that would eliminate the need for lifelong insulin injections—is in high demand. Stem cell-based therapies have been considered, but they raise the risk of tumors that can develop from residual immature cells. And while donor islet cells have been transplanted in experimental treatments, they almost always fail, even when given along with drugs that suppress immune reactions.
"Drugs that allow the transplantation of the islet cells are toxic to them," said Andrés García, a professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering. "Clinical trials with transplantation of islets showed effectiveness, but after a few years, the grafts were rejected. There is a lot of hope for this treatment, but we just can't get consistent improvement."
Another problem with islet transplants is that they often lose their blood vessels and do not engraft properly in the patient. García's lab has shown that it can stimulate blood vessel growth into cells transplanted into the fat pad in mice. In humans, transplants could be delivered into the omentum, a tissue similar to this fat pad.
Other work to improve cell therapies for diabetes include a new culture method that promotes the vascularization of islets created from stem cells and a regenerative approach that involves tapping into a "bank" of pancreatic stem cells that can develop into insulin-producing cells for transplant.
Gene therapy is another potential option: University of Pittsburgh scientists delivered a pair of proteins to the pancreas in mice, "reprogramming" alpha cells into insulin-producing beta cells.
The Georgia Tech scientists and their research partners are now testing their hydrogel-enabled islet transplant approach in nonhuman primates. They believe that if the procedure proves useful in people, it will be relatively easy to scale up and make widely available to patients with diabetes.
"The key technical advance is the ability to make this material that induces immune acceptance that can simply be mixed with the islets and delivered," Garcia said. "We can make the biomaterial in our lab and ship them to where the transplantation will be done, potentially making it an off-the-shelf therapeutic,"