Protecting insulin-producing cells from immune system gives benefits of transplant to resolve diabetes without drawbacks of anti-rejection drugs
Type I diabetes is often diagnosed in childhood and can be devastating. Unable to produce insulin in their own bodies to metabolise glucose, children must depend on regular injections of insulin, with doses determined by blood tests several times a day, to avoid falling into a coma as blood sugar levels drop; moreover, the long-term damage caused by abnormal sugar levels can be severe.
“The absence of this natural ability – minute-to-minute regulation of glucose levels – can result in long-term complications, such as blindness, amputation and kidney failure,” explained Dr Klearchos Papas of the Departments of Surgery and Medical Imaging at the University of Arizona College of Medicine – Tucson. “Even with automated insulin delivery devices and continuous glucose monitoring – the best way possible to control your blood sugar – you still can end up with these consequences.”
One method of controlling type I diabetes that has been investigated in depth is transplanting insulin-producing cells, known as islets, into the liver. If accepted, these sense glucose levels and secrete insulin into the bloodstream to break it down. But in common with all transplants, donors must take drugs to suppress their immune systems to prevent rejection. The side effects of these drugs are unpleasant and can be dangerous, so this technique is not recommended for children.
Papas and his team have been researching this problem for the past two decades, and in collaboration with chemicals company Novo Nordisk and other researchers in the US, Canada and Australia, has found a solution which blends engineering with cell science. The key to the technique is to place the islet cells inside an implantable, porous container. In the journal Endocrine Connections, the researchers explain how they keep the cells alive inside the container made of a silicone-based organic polymer, polydimethylsiloxane. “It’s like a tea bag,” Papas said. “The tea leaves stay inside but tea, or insulin, comes out. And the tea bag keeps out the immune cells that would normally attack the islets.”
This concept is not new, but Papas’ team believes it has cracked one of the major blocks that has prevented it from succeeding in the past: miniaturising the teabag and keeping the islet cells alive. The key to this is another implant, which feeds oxygen to the isolated cells.
“The unique thing we bring to the table is the combination of an optimised tea bag with its own oxygen supply,” Papas explained. “Islets are happier with an oxygen supply; they survive and function better and this has been overlooked in the past.”
The battery-powered oxygen generator the team has developed is the size of a stack of 10p pieces. It could be implanted under the skin of the arm or back, and recharged wirelessly via an induction technique. Papas hopes to be able to start clinical trial within 3 to 4 years. “This is not pie-in-the-sky crazy science,” he said. “We believe, engineering-wise, it is achievable. The cells and the biology were the difficult part and they have come a long way in the past five years.”
Novo Nordisk is currently working on generating islets from human stem cells rather than taking them from donors, which would help produce enough of the cells to treat the number of potential patients.
“This is an incredible example of the kind of innovative and collaborative research that is taking place on the UA campus that has only recently become possible with the convergence of the physical, biological and digital worlds,” commented University of Arizona president Robert Robbins. “The work that Dr. Papas and his team are doing to help children with diabetes is a great example of using new technology to significantly improve quality of life for patients.”