Diabetic Device Replaces Injections || Regulates Insulin

One promising approach to treating Type 1 diabetes is implanting pancreatic islet cells that can produce insulin when needed, which can free patients from giving themselves frequent insulin injections. However, one major obstacle to this approach is that once the cells are implanted, they eventually run out of oxygen and stop producing insulin.

To overcome that hurdle, MIT engineers have designed a new implantable device that not only carries hundreds of thousands of insulin-producing islet cells, but also has its own on-board oxygen factory, which generates oxygen by splitting water vapor found in the body.

The researchers showed that when implanted into diabetic mice, this device could keep the mice's blood glucose levels stable for at least a month. The researchers now hope to create a larger version of the device, about the size of a stick of chewing gum, that could eventually be tested in people with Type 1 diabetes.

"You can think of this as a living medical device that is made from human cells that secrete insulin, along with an electronic life support-system. We're excited by the progress so far, and we really are optimistic that this technology could end up helping patients," says Daniel Anderson, a professor in MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.

While the researchers' main focus is on diabetes treatment, they say that this kind of device could also be adapted to treat other diseases that require repeated delivery of therapeutic proteins.

MIT Research Scientist Siddharth Krishnan is the lead author of the paper, which appears today in the Proceedings of the National Academy of Sciences. The research team also includes several other researchers from MIT, including Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, as well as researchers from Boston Children's Hospital.

Replacing injections

Most patients with Type 1 diabetes have to monitor their blood glucose levels carefully and inject themselves with insulin at least once a day. However, this process doesn't replicate the body's natural ability to control blood glucose levels.

"The vast majority of diabetics that are insulin-dependent are injecting themselves with insulin, and doing their very best, but they do not have healthy blood sugar levels," Anderson says. "If you look at their blood sugar levels, even for people that are very dedicated to being careful, they just can't match what a living pancreas can do."

A better alternative would be to transplant cells that produce insulin whenever they detect surges in the patient's blood glucose levels. Some diabetes patients have received transplanted islet cells from human cadavers, which can achieve long-term control of diabetes; however, these patients have to take immunosuppressive drugs to prevent their body from rejecting the implanted cells.

More recently, researchers have shown similar success with islet cells derived from stem cells, but patients who receive those cells also need to take immunosuppressive drugs.

Another possibility, which could prevent the need for immunosuppressive drugs, is to encapsulate the transplanted cells within a flexible device that protects the cells from the immune system. However, finding a reliable oxygen supply for these encapsulated cells has proven challenging.

Some experimental devices, including one that has been tested in clinical trials, feature an oxygen chamber that can supply the cells, but this chamber needs to be reloaded periodically. Other researchers have developed implants that include chemical reagents that can generate oxygen, but these also run out eventually.

The MIT team took a different approach that could potentially generate oxygen indefinitely, by splitting water. This is done using a proton-exchange membrane -- a technology originally deployed to generate hydrogen in fuel cells -- located within the device. This membrane can split water vapor (found abundantly in the body) into hydrogen, which diffuses harmlessly away, and oxygen, which goes into a storage chamber that feeds the islet cells through a thin, oxygen-permeable membrane.

A significant advantage of this approach is that it does not require any wires or batteries. Splitting this water vapor requires a small voltage (about 2 volts), which is generated using a phenomenon known as resonant inductive coupling. A tuned magnetic coil located outside the body transmits power to a small, flexible antenna within the device, allowing for wireless power transfer. It does require an external coil, which the researchers anticipate could be worn as a patch on the patient's skin.