Cell Implant Device Could Control Type 1 Diabetes

A majority of diabetes patients have to carefully monitor their glucose levels and inject multiple times per day in order to keep their blood sugar from rising to an unsafe level.

Massachusetts Institute of Technology (MIT) researchers reported that they are building an implantable device that contains insulin-producing cells, also known as islet cells. This device encapsulates the cells, protecting them from immune rejection. It also features an on-board oxygen generator to ensure the cells remain healthy.

The researchers hope the device can provide a means to gain long-term control of type 1 diabetes. In a new study, the MIT team demonstrated that the encapsulated pancreatic islet cells could survive in the body for at least 90 days. The cells stayed functional in mice that received the implants and produced enough insulin to control the animals’ glucose 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,” 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 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 published recently in the journal Device. Former MIT research scientist Siddharth Krishnan, 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.

Transplantation of islet cells has already been successfully used to treat diabetes in patients. The cells usually come from human cadavers, or more recently, created from stem cells. In both cases, patients have to take immunosuppressive drugs in order to prevent their immune system from rejecting the transplanted cells.

An alternative method to prevent immune rejection is to house the cells in a protective device, but the coating that surrounds the cells can stop them from receiving enough needed oxygen.

Three years ago, Anderson and his colleagues described a pancreatic islet-encapsulation device that carries an on-board oxygen generator. The generator is made of a proton-exchange membrane that can split water vapor, which is found quite a bit in the body, into hydrogen and oxygen. The hydrogen diffuses away and oxygen moves into a storage chamber that feeds the islet cells through a thin, oxygen-permeable membrane.

The researchers discovered that cells encapsulated in this device could produce insulin for up to a month after implantation into 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 said.

This new study witnessed the MIT researchers growing the devices’ lifespan by rendering them more waterproof and more resilient against cracking. They also bolstered the device’s electronics in order to provide more power to the oxygen generator.

An external antenna placed on the skin wirelessly powers the implant and transfers energy to the device. Fine-tuning the circuitry let the researchers increase the power reaching the oxygen-generating system.

In more rat and mice studies, the researchers demonstrated the new device was able to function for at least 90 days after implantation under the skin. The donor islet cells could produce enough insulin to keep the animals’ blood sugar within range during this time.

Similar results were seen with islet cells derived from induced pluripotent stem cells. These could one day offer an indefinite supply that may be used for any patient needing them. The researchers said the islets didn’t fully reverse diabetes but 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 said. The researchers will now study if they can get the devices to last up to two years or more in the body.

“Long-term survival of the islets is an important goal,” said Anderson. “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 using this method to deliver cells that could produce other proteins like 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 concluded. “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.”