For decades, researchers have tried to duplicate the function of beta cells, the tiny insulin-producing entities that don’t work properly in patients with diabetes. Insulin injections provide painful and often imperfect substitutes. Transplants of normal beta cells carry the risk of rejection or side effects from immunosuppressive therapies.
Now, researchers at the University of North Carolina (UNC) at Chapel Hill and North Carolina State University (NC State) have devised another option: a synthetic patch filled with natural beta cells that can secrete doses of insulin to control blood sugar levels on demand with no risk of inducing hypoglycemia.
The proof of concept builds on an innovative technology, the smart insulin patch, reported last year in the Proceedings of the National Academy of Sciences. Both patches are thin polymeric squares about the size of a quarter and covered in tiny needles, like a miniature bed of nails. But this new “smart cell patch” integrates the needles with live beta cells.
Tests of this painless patch in small animal models of type 1 diabetes demonstrated that it could quickly respond to skyrocketing blood sugar levels and significantly lower them for ten hours at a time. The results were published in Advanced Materials.
Beta cells typically reside in the pancreas, where they act as the body’s natural insulin-producing factories. In healthy people, they produce, store, and release the hormone insulin to help process sugar that builds up in the bloodstream after a meal. But in people with diabetes, these cells are either damaged or unable to produce enough insulin to keep blood sugar levels under control.
Since the 1970s, researchers have researched transplantation of insulin-producing cells as an alternative treatment for diabetes. The first successful transplant of human beta cells was performed in 1990, and since then hundreds of diabetic patients have undergone the procedure. Yet only a fraction of treated patients achieved normal blood sugar levels. Most transplants are rejected, and many of the medications used to suppress the immune system wind up interfering with the activity of beta cells and insulin. Lead author Yanqi Ye, a graduate student, constructed the smart cell patches and stuffed the hundreds of microneedles with culture media and thousands of beta cells that were encapsulated into microcapsules made from biocompatible alginate. When applied to the skin, the patch’s microneedles poked into the capillaries and blood vessels, forming a connection between the internal environment and the external cells of the patch.
The research group, led by senior author Zhen Gu, PhD, assistant professor in the joint UNC/NC State department of biomedical engineering, showed that blood sugar levels in mice with diabetes quickly declined to normal levels. To assess whether the patch could regulate blood sugar without lowering it too much, the researchers administered a second patch to the mice. As they had hoped, repeated administration of the patch did not result in excess doses of insulin, and thus did not risk hypoglycemia. Instead, the second patch extended the life of the treatment to 20 hours.
Further modifications, preclinical tests, and eventually clinical trials in humans will all be necessary before the patch can become a viable option for patients.
This article was adapted from information provided by UNC Health Care.
