MIT engineers have developed a breakthrough device to treat type 1 diabetes that is designed to replace daily insulin injections. The implantable device houses insulin-producing cells and produces oxygen by splitting the body's water vapor. When tested on diabetic mice, the device successfully maintained the mice's blood sugar levels for more than a month. The device contains encapsulated cells that produce insulin and a tiny oxygen-producing factory that keeps the cells healthy.
One promising approach to treating type 1 diabetes is to implant pancreatic islet cells that produce insulin when needed, so patients don't have to inject insulin as frequently. However, a major obstacle to this approach is that once the cells are implanted, they eventually stop producing insulin due to lack of oxygen.
To overcome this obstacle, MIT engineers designed a new implantable device that not only carries hundreds of thousands of insulin-producing islet cells, but also has its own onboard oxygen factory that produces oxygen by splitting water in the body.
The researchers' results showed that implanting the device into diabetic mice kept their blood sugar levels stable for at least a month. The researchers now hope to create a larger version of the device, about the size of a piece of chewing gum, and eventually test it on people with type 1 diabetes.
Insights from the research team
"You can think of it as a living medical device made up of insulin-producing human cells and electronic life support systems," said Daniel Anderson, a professor in MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science (IMES), and senior author of the study. "We're excited about the progress we're making so far, and we're very optimistic that this technology can ultimately help patients."
While the researchers' main focus is on diabetes treatment, they say the device could also be used to treat other diseases that require repeated delivery of therapeutic proteins.
MIT research scientist Siddharth Krishnan is the first author of the paper, which was recently published in the Proceedings of the National Academy of Sciences. The research team also included several other MIT researchers, including Robert Langer, a professor at MIT's David Koch Institute and a member of the Koch Institute, as well as researchers at Boston Children's Hospital.
Current Challenges in Diabetes Treatment
Most people with type 1 diabetes must monitor their blood sugar levels carefully and inject insulin at least once a day. However, this process does not replicate the body's natural ability to control blood sugar levels.
"The vast majority of people with insulin-dependent diabetes are injecting themselves with insulin and doing their best, but their blood sugar levels are not healthy," Anderson said. "If you look at their blood sugar levels, even in people who are very conscientious and careful, their blood sugar levels are not comparable to a living pancreas."
A better alternative would be to transplant cells that produce insulin whenever a spike in a patient's blood sugar levels is detected. Some diabetic patients have achieved long-term control of their diabetes by receiving transplants of islet cells from human cadavers; however, these patients must take immunosuppressive drugs to prevent the body from rejecting the implanted cells.
More recently, researchers have had similar success using islet cells derived from stem cells, but patients who receive these cells also need to take immunosuppressants.
Addressing Oxygen Supply Challenges
Another way to avoid the use of immunosuppressants is to encapsulate transplanted cells in a flexible device that protects the cells from the immune system. However, finding a reliable supply of oxygen for these encapsulated cells has proven challenging.
Some experimental devices, including one already being tested in clinical trials, have an oxygen chamber that supplies cells with oxygen, but the chamber needs to be reloaded periodically. Other researchers have developed implants that include chemical agents that produce oxygen, but these agents also eventually run out.
The MIT team took another approach, creating unlimited oxygen production by splitting water. This method is achieved through a proton exchange membrane within the device, a technology originally used to generate hydrogen in fuel cells. This membrane separates water vapor (which is abundant in the human body) into hydrogen and oxygen. The hydrogen diffuses harmlessly, while the oxygen enters a storage chamber and is supplied to the islet cells through a thin oxygen-permeable membrane.
A big advantage of this method is that it doesn't require any wires or batteries. Separating this water vapor requires a small voltage (about 2 volts), which is generated using a phenomenon called resonant inductive coupling. Tuned magnetic coils located outside the body transmit power to a small, flexible antenna within the device, enabling wireless power transfer. It requires an external coil, which researchers envision could be worn as a patch on a patient's skin.
Promising experimental results
After creating a device about the size of a U.S. quarter, the researchers tested it on diabetic mice. One group of mice received a device with oxygen-generating and water-separating membranes, and another group received a device containing islet cells but without supplemental oxygen. The devices were implanted subcutaneously in mice with fully functional immune systems.
The researchers found that mice implanted with oxygen-generating devices were able to maintain normal blood sugar levels, comparable to healthy animals. However, mice that received the non-oxygenated device developed hyperglycemia (increased blood sugar) within about two weeks.
Typically, after any kind of medical device is implanted in the body, an attack by the immune system causes a buildup of scar tissue, known as fibrosis, that reduces the device's effectiveness. This scar tissue did form around the implant used in this study, but the device successfully controlled blood sugar levels, suggesting that insulin was still able to diffuse out of the device and glucose was able to enter it.
This approach could also be used to deliver cells that produce other types of therapeutic proteins that require long-term administration. In the study, the researchers found that the device also kept alive cells that produce erythropoietin, a protein that stimulates the production of red blood cells.
future outlook
"We're optimistic that it's possible to create living medical devices that can reside in the body and produce drugs on demand," Anderson said. "There are a variety of diseases where patients need to take proteins exogenously, sometimes frequently. If we could replace the need for infusions every other week with an implant that works long-term, I think that could really help a lot of patients."
The researchers now plan to adapt the device to test it on larger animals and eventually humans. For human use, they hope to develop an implant about the size of a piece of chewing gum. They also plan to test whether the device can remain in the body longer.
"The materials we're using are inherently stable and long-lasting, so I think long-term operation of this kind is possible and that's what we're working on," Krishnan said.
"We are very excited about these findings, which we believe will one day provide an entirely new way to treat diabetes and other diseases," Langer added.
This research was supported by grants from JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.