Biomaterial improves islet transplants for treatment of type 1 diabetes

Islet 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 sustainable and tightly 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 reject the foreign invaders.

But a team of investigators overcame this hurdle in previous small animal studies. Their technique 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 safely do their job, regulating blood glucose levels, and fighting diabetes.

A new study in the journal Science Advances from the researchers moves this hopeful treatment strategy closer to the clinic.

“Immunosuppression is a significant problem for patients, but in our prior work we showed that this biomaterial, this microgel, is a potent immunomodulatory molecule, and can induce permanent acceptance of the new cells,” said the senior author.

“But that study was done in mice, and the immune system of a mouse if very different from a human’s,” the author added. “And in the progression toward clinical use, you really need to test this strategy in a large animal model.”

Their study demonstrates how co-transplanting islet cells with SA-FasL-microgels reversed diabetic symptoms while overcoming the immune response in nonhuman primates. The researchers without using immunosuppressants, which can have dangerous side effects.  

The microgels essentially teach the immune system to accept the graft, interrupting the body’s inclination to reject the transplant and circumventing the need for continuous immunosuppression.

“Those immunosuppressive regimens are toxic to the patient, so a major goal in the field has been to develop approaches that will allow you to put in this graft and get it to function without chronic immunosuppression,” said the author.

Because the biomaterial can be created in a lab and shipped anywhere, the new therapeutic is essentially off-the-shelf. And now that they’ve proven the strategy works in nonhuman primates, the authors are confident that patients with type 1 diabetes could have a powerful new treatment option.