Islet cell transplantation is a promising treatment that can cure type 1 diabetes that is difficult to treat. Cells taken from the donor pancreas provide patients with a stable and strictly controlled source of insulin. The main problem is to force the patient’s immune system to accept the influx of new donor cells; the patient’s protective T cells naturally want to repel foreign invaders.
But a team of researchers led by Georgia Institute of Technology researcher Andres Garcia has overcome that hurdle in previous research on small animals. Their technique uses synthetic hydrogel particles called microgels. Microgels are a powerful immunomodulatory protein called SA-FasL to modulate the body’s immune response, allowing transplanted insulin-producing cells to safely do their job by regulating blood glucose levels and battling diabetes.
A new study in the journal Advances in science from Garcia and his staff moves this encouraging 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 powerful immunomodulatory molecule and can cause the constant uptake of new cells,” said Garcia, chairman of Bioengineering and Regents. Professor of the George Woodruff School of Mechanical Engineering and Executive Director of the Petit Institute of Bioengineering and Biosciences.
“But this study was done on mice, and the mouse’s immune system is very different from the human,” Garcia added. “And in progressing to clinical use you really need to test this strategy on large animal models.”
Now they have. Garcia and his fellow researchers from the University of Missouri and Massachusetts General Hospital explain their findings in a new paper.
Their study, funded by the Juvenile Diabetes Research Foundation, demonstrates how co-transplantation of islet cells using SA-FasL microgels reduced diabetes symptoms by overcoming the immune response in primates. The researchers did not use immunosuppressants that could have dangerous side effects.
Microgels, in fact, teach the immune system to accept the transplant, interrupting the body’s tendency to refuse transplantation and bypassing the need for constant immunosuppression.
“These immunosuppressive regimens are toxic to the patient, so the main goal in this area was to develop approaches that would allow you to deliver this graft and make it function without chronic immunosuppression,” Garcia said.
Because the biomaterial can be created in the lab and shipped anywhere, the new therapeutic drug is essentially ready. And now that they have proven that the strategy works in non-human primates, Garcia and his staff are confident that patients with type 1 diabetes can have a new powerful treatment option.
Garcia is the co-founder of the company that licensed the technology, iTolerance, which is already discussing plans for human clinical trials with the U.S. Food and Drug Administration.
“We’re very filled – it’s very exciting, and it’s encouraging results for people struggling with type 1 diabetes,” said Garcia, author-correspondent and part of a research team of 20 people. “This work would be impossible with such an approach to team science.”
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