A team of scientists has created synthetic pancreatic beta cells that automatically release insulin when they sense high blood sugar.
In the journal Nature Chemical Biology, researchers from the University of North Carolina at Chapel Hill and North Carolina State University in Raleigh describe how they developed and tested the synthetic cells.
Senior author Zhen Gu, a professor in biomedical engineering at both universities, and team hope that one day, the cells could be used in a noninvasive skin patch to treat diabetes.
They found that just one injection of the synthetic beta cells kept blood sugar in diabetic mice at normal levels for 5 days.
The body produces insulin in the pancreas, which is a glandular organ behind the stomach that houses the beta cells that make and release the right amount of the hormone, depending on glucose levels.
Around 6 million of the 30 million people in the United States with diabetes manage the disease using insulin treatments, either by regular injections or with infusion pumps.
Over the years, there have been attempts to develop a pill form of insulin treatment, but they have encountered problems — including the fact that the body’s strong digestive system breaks down the large molecules in the pill before they make it to the bloodstream.
It is also possible to treat some cases of diabetes with transplanted pancreatic cells. However, these treatments are costly, need drugs that suppress immune reactions to the transplant, and rely on donated tissue, which is scarce. There is also a high risk that the transplanted cells will perish anyway.
In their study paper, the scientists explain that biological engineers have made several attempts to “recreate the key functions” of pancreatic beta cells for therapeutic purposes. They give examples, such as nanoparticles cloaked in cell membranes and microgels that slowly release drugs.
But a common problem with previous approaches to mimic beta cells is their “single-compartment” structure and their “relatively passive” way of interacting with the biology of the body, note the authors.
Some researchers have tried to create multicompartment structures to mimic beta cells — for instance, to deliver a mixture of drugs or produce a cascading effect.
But none so far have managed to “mimic the higher-order functions” of the natural beta cells whose sophisticated systems “can precisely sense the external environment, make internal decisions, and trigger feedback.”
The new study marks nearly a decade of work in which Prof. Gu and his team have been wrestling with this problem. The result is a synthetic beta cell that very closely mimics the key processes of natural pancreatic beta cells.
The synthetic beta cell has a simple double-membrane cell wall made of lipids, inside which are vesicles, or small sacs, full of insulin. In addition to the “vesicle-in-vesicle” structure there is a “glucose-metabolism system and membrane-fusion machinery.”
When the glucose-metabolism system senses a rise in glucose levels, it triggers changes in the coating of the vesicles so that they begin to fuse with the outer membrane of the cell and release the insulin inside them.
“To our knowledge,” note the authors, “this synthetic system is the first of its kind that can sense glucose levels and readily secrete insulin through vesicle-fusion-mediated behavior.”
So far, the researchers have tested the synthetic beta cells in the laboratory and in diabetic mice lacking beta cells.
“The mice went from hyperglycemic to normoglycemic within an hour,” Prof. Gu explains, “and they remained normoglycemic for up to 5 days after that.”
In contrast, injecting diabetic mice with synthetic beta cells that did not carry insulin did not bring down their high blood sugar levels.
The team now plans to carry out further tests with a view to developing a painless treatment that delivers synthetic beta cells using a skin patch.
Prof. Gu’s group is already developing a “smart insulin patch” that does not use cells but senses levels of blood sugar and automatically delivers insulin into the bloodstream.
They point out that there is still a lot of work to do before the synthetic cells can be tested in humans.
“Our plan now is to further optimize and test these synthetic cells in larger animals, develop a skin patch delivery system for them, and ultimately test them in people with diabetes.”
Prof. Zhen Gu