Most diabetes patients must carefully monitor their blood sugar levels and inject insulin multiple times per day, to help keep their blood sugar from getting too high.
As a possible alternative to those injections, MIT researchers are developing an implantable device that contains insulin-producing cells. The device encapsulates the cells, protecting them from immune rejection, and it also carries an on-board oxygen generator to keep the cells healthy.
This device, the researchers hope, could offer a way to achieve long-term control of type 1 diabetes. In a new study, they showed that these encapsulated pancreatic islet cells could survive in the body for at least 90 days. In mice that received the implants, the cells remained functional and produced enough insulin to control the animals’ blood sugar levels.
“Islet cell therapy can be a transformative treatment for patients. However, current methods also require immune suppression, which for some people can be really debilitating,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science. “Our goal is to find a way to give patients the benefit of cell therapy without the need for immune suppression.”
Anderson is the senior author of the study, which appears today in the journal Device. Former MIT research scientist Siddharth Krishnan, who is now an assistant professor of electrical engineering at Stanford University, and former MIT postdoc Matthew Bochenek are the lead authors of the paper. Robert Langer, the David H. Koch Institute Professor at MIT, is also a co-author.
Insulin on demand
Islet cell transplantation has already been used successfully to treat diabetes in patients. Those islet cells typically come from human cadavers, or more recently, can be generated from stem cells. In either case, patients must take immunosuppressive drugs to prevent their immune system from rejecting the transplanted cells.
Another way to prevent immune rejection is to encapsulate cells in a protective device. However, this raises new challenges, as the coating that surrounds the cells can prevent them from receiving enough oxygen.
In a 2023 study, Anderson and his colleagues reported an islet-encapsulation device that also carries an on-board oxygen generator. This generator consists of a proton-exchange membrane that can split water vapor (found abundantly in the body) into hydrogen and oxygen. The hydrogen diffuses harmlessly away, while oxygen goes into a storage chamber that feeds the islet cells through a thin, oxygen-permeable membrane.
Cells encapsulated within this device, they found, could produce insulin for up to a month after being implanted in mice.
“A month is a good timeframe in that it shows basic proof-of-concept. But from a translational standpoint, it’s important to show that you can go quite a bit longer than that,” Krishnan says.
In the new study, the researchers increased the lifespan of the devices by making them more waterproof and more resilient to cracking. They also improved the device electronics to deliver more power to the oxygen generator. The implant is powered wirelessly by an external antenna placed on the skin, which transfers energy to the device. By optimizing the circuitry, the researchers were able to increase the amount of power reaching the oxygen-generating system.
The additional power allowed the device to produce more oxygen, helping the encapsulated cells to survive and function more effectively. As a result, the cells were able to generate much more insulin over time.
Protein factories
In studies in rats and mice, the researchers showed that the new device could function for at least 90 days after being implanted under the skin. During this time, donor islet cells were able to produce enough insulin to keep the animals’ blood sugar levels within a healthy range.
The researchers saw similar results with islet cells derived from induced pluripotent stem cells, which could one day provide an indefinite supply that could be used for any patient who needs them. These islets didn’t fully reverse diabetes, but they did achieve some control of blood sugar levels.
“We’re hoping that in the future, if we can give the cells a little bit longer to fully mature, that they’ll secrete even more insulin to better regulate diabetes in the animals,” Bochenek says.
The researchers now plan to study whether they can get the devices to last for even longer in the body — up to two years, or longer.
“Long-term survival of the islets is an important goal,” Anderson says. “The cells, if they’re in the right environment, seem to be able to survive for a long time. We are excited by the duration we’ve already achieved, and we will be working to extend their function as long as possible.”
The researchers are also exploring the possibility of using this approach to deliver cells that could produce other useful proteins, such as antibodies, enzymes, or clotting factors.
“We think that these technologies could provide a long-term way to treat human disease by making drugs in the body instead of outside of the body,” Anderson says. “There are many protein therapies where patients must receive repeated, lengthy infusions. We think it may be possible to create a device that could continuously create protein therapeutics on demand and as needed by the patient.”
The research was funded, in part, by Breakthrough TID, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and a Koch Institute Support (core) Grant from the National Cancer Institute.
