Implantable device allow injection-free diabetes management

Implanting pancreatic islet cells that can manufacture insulin when needed is one promising technique for treating Type 1 diabetes, which could liberate patients from needing regular insulin injections. However, once the cells are transplanted, they eventually run out of oxygen and cease generating insulin.

The study was published in Proceedings of the National Academy of Science.

To overcome this hurdle, MIT researchers created a unique implantable device that not only contains hundreds of thousands of insulin-producing islet cells but also has its own onboard oxygen factory that manufactures oxygen by splitting water vapour found in the body.

When implanted into diabetic mice, the researchers demonstrated that this device could maintain the mice's blood glucose levels steady for at least a month. The researchers are now hoping to develop a larger version of the device, around the size of a stick of chewing gum, that will be tested in persons 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,” said 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.

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 said.

“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 bodies 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.

A significant advantage of this approach is that it does not require any wires or batteries. Splitting this water vapour 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.

After building their device, which is about the size of a U.S. quarter, the researchers tested it in diabetic mice. One group of mice received the device with the oxygen-generating, water-splitting membrane, while the other received a device that contained islet cells without any supplemental oxygen. The devices were implanted just under the skin, in mice with fully functional immune systems.

The researchers found that mice implanted with the oxygen-generating device were able to maintain normal blood glucose levels, comparable to healthy animals. However, mice that received the nonoxygenated device became hyperglycemic (with elevated blood sugar) within about two weeks.

Typically when any kind of medical device is implanted in the body, an attack by the immune system leads to a buildup of scar tissue called fibrosis, which can reduce the devices’ effectiveness. This kind of scar tissue did form around the implants used in this study, but the device’s success in controlling blood glucose levels suggests that insulin was still able to diffuse out of the device, and glucose into it.

This approach could also be used to deliver cells that produce other types of therapeutic proteins that need to be given over long periods of time.

“We’re optimistic that it will be possible to make living medical devices that can reside in the body and produce drugs as needed,” Anderson said.

In this study, the researchers showed that the device could also keep alive cells that produce erythropoietin, a protein that stimulates red blood cell production.

“There are a variety of diseases where patients need to take proteins exogenously, sometimes very frequently. If we can replace the need for infusions every other week with a single implant that can act for a long time, I think that could really help a lot of patients.”

 “The materials we’ve used are inherently stable and long-lived, so I think that kind of long-term operation is within the realm of possibility, and that’s what we’re working on,” Krishnan said.

“We are very excited about these findings, which we believe could provide a whole new way of someday treating diabetes and possibly other diseases,” Langer added.