Island cell transplants are a promising treatment that can cure difficult-to-treat type 1 diabetes. The cells, taken from a donor pancreas, provide patients with a durable and carefully controlled source of insulin. A major problem is getting the patient’s immune system to accept the influx of new donor cells; the patient’s protective T cells naturally want to repel the foreign invaders.
But a team of investigators led by researcher at the Georgia Institute of Technology, Andrés García, overcame this obstacle in previous studies on small animals. Their technology uses synthetic hydrogel particles called microgels. The microgels present a potent immunomodulatory protein called SA-FasL to modulate the body’s immune response, allowing the transplanted insulin-producing cells to do their job safely, regulate blood sugar levels and fight diabetes.
A new study in the journal The progress of science from García and his staff moves this hopeful treatment strategy closer to the clinic.
“Immunosuppression is a significant problem for patients, but in our previous work we showed that this biomaterial, this microgel, is a potent immunomodulatory molecule and can induce permanent acceptance of the new cells,” said García, Petit Chair in Bioengineering and Regents Professor at George W. Woodruff School of Mechanical Engineering and Executive Director of the Petit Institute for Bioengineering and Bioscience.
“But that study was done on mice, and the immune system of a mouse if it is very different from a human,” García added. “And in the development towards clinical use, you really have to test this strategy in a large animal model.”
Now they have it. García and his research colleagues from the University of Missouri and Massachusetts General Hospital explain their findings in the new article.
Their study, funded by the Juvenile Diabetes Research Foundation, shows how co-transplantation of islets with SA-FasL microgels reversed diabetic symptoms while overcoming the immune response in non-human primates. Researchers without the use of immunosuppressive agents, which can have dangerous side effects.
The microgels mainly teach the immune system to accept the graft, which interrupts the body’s tendency to reject the graft and circumvents the need for continuous immunosuppression.
“These immunosuppressive regimens are toxic to the patient, so a major goal in this area has been to develop methods that allow you to inject this graft and make it work without chronic immunosuppression,” says García.
Because the biomaterial can be created in a lab and sent anywhere, the new therapeutic agent is basically a shelf. And now that they’ve proven that the strategy works in non-human primates, García and his staff are convinced that patients with type 1 diabetes can be given a powerful new treatment option.
García is one of the founders of the company that licensed the technology, iTolerance, which is already discussing plans for clinical trials on humans with the US Food and Drug Administration.
“We’m pretty pumped up – this is very exciting, and these are hopeful results for people fighting type 1 diabetes,” said García, co-author and part of a 20-person research team. “This work would not have been possible with this team science strategy.”