By Ann Trafton | MIT News
Most people with diabetes must monitor their blood sugar levels carefully and inject insulin multiple times a 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 also carries an on-board oxygen generator to keep the cells healthy.
Researchers hope the device 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 can survive in the body for at least 90 days. In the mice that received the implants, the cells were viable and produced enough insulin to control the animals’ blood sugar levels.
“Islet cell therapy could be a transformative treatment for patients. However, current methods also require immune suppression, which can be really debilitating for some people,” said 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 ways to benefit patients with cell therapy without the need for immune suppression.”
Anderson is senior author of the study, which Appeared in the journal today device. Former MIT research scientist Siddharth Krishnan, now an assistant professor of electrical engineering at Stanford University, and former MIT postdoc Matthew Bochenek are lead authors of the paper. Robert Langer, a professor at MIT’s David H. Koch Institute, is also a co-author.
Insulin on demand
Islet cell transplantation has already been used successfully to treat diabetes in patients. These islet cells usually come from a human cadaver, or more recently, can be made from stem cells. In both cases, patients must take immunosuppressive drugs to prevent their immune system from rejecting the transplanted cells.
Another way to prevent immune rejection is to enclose the cells in a protective mechanism. However, this raises new challenges, as the membrane that surrounds cells can prevent them from receiving enough oxygen.
In a 2023 study, Anderson and colleagues reported an islet-encapsulation device It also carries an on-board oxygen generator. This generator contains a proton-exchange membrane that can split water vapor (found in abundance in the body) into hydrogen and oxygen. Hydrogen diffuses away harmlessly, while oxygen moves into a storage chamber that feeds islet cells through a thin, oxygen-permeable membrane.
They found that the cells inside the device could produce insulin for up to a month after being implanted in mice.
“One month is a good time frame where it shows basic proof of concept. But from a translational point of view, it’s important to show that you can go quite a bit longer than that,” says Krishnan.
In the new study, the researchers extended the lifespan of the devices by making them more waterproof and more resilient to cracking. They improved the device electronics to deliver more power to the oxygen generator. The implant is powered wirelessly by an external antenna placed in the skin, which transfers energy to the device. By optimizing the circuitry, the researchers were able to increase the amount of energy reaching the oxygen-producing system.
The extra energy allows the device to produce more oxygen, helping the encapsulated cells survive and function more effectively. As a result, the cells were able to produce much more insulin over time.
protein factory
In studies on mice and rats, the researchers showed that the new device could work for at least 90 days after being implanted under the skin. During this time, the 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 did not completely 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 more time to fully mature, that they’ll release more insulin to better control diabetes in animals,” Bochenek said.
Researchers now plan to study whether they can keep the devices in the body for longer — up to two years or more.
“The long-term survival of the islands is an important goal,” Anderson said. “Cells, if they’re in the right environment, seem to be able to survive for a long time. We’re excited about the time we’ve already achieved, and we’ll work to extend their viability as long as possible.”
Researchers are also exploring the possibility of using this method to deliver cells that can produce other useful proteins such as antibodies, enzymes or clotting factors.
“We think these technologies could provide a long-term way to treat human disease by making drugs inside the body instead of outside the body,” Anderson said. “There are many protein therapies that require patients to take repeated, long infusions. We think it may be possible to develop a device that can continuously produce protein therapeutics on demand and as the patient needs them.”
The study, in part, breakthrough TID, Leona M. and Harry B. was funded by a Koch Institute Support (CORE) grant from the Helmsley Charitable Trust, the National Institutes of Health and the National Cancer Institute.
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Reprinted with permission MIT News
Image: splash
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