A potential method for addressing Type 1 diabetes involves the insertion of pancreatic islet cells capable of producing insulin as needed, thereby eliminating the need for regular insulin injections. However, a significant challenge with this approach is that once implanted, these cells eventually become deprived of oxygen, leading to a halt in
. This device houses hundreds of thousands of insulin-producing islet cells and incorporates its own internal oxygen generator, which produces oxygen by splitting water vapor
The team demonstrated that upon implantation into diabetic mice, this device effectively maintained stable blood glucose levels for at least a month. The researchers aspire to develop a larger version of the device, approximately the size of a stick of chewing gum, for eventual testing in individuals with Type 1 diabetes.
Daniel Anderson, a professor at 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 (IMES), who serves as the senior author of the study, explains, “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.”
While the primary focus of the researchers is on diabetes treatment, they suggest that this type of device could also be adapted to address other conditions necessitating repeated administration of therapeutic proteins.
The lead author of the paper, titled “Replacing injections,” is MIT Research Scientist Siddharth Krishnan. The study, published in the Proceedings of the National Academy of Sciences, includes contributions from various other researchers at MIT, including Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, as well as researchers from Boston Children’s Hospital.
In Type 1 diabetes, patients typically have to meticulously monitor their blood glucose levels and administer insulin injections at least once daily. However, this process does not replicate the body’s natural ability to regulate blood glucose levels.
The preferred alternative would involve transplanting cells capable of producing insulin in response to spikes in the patient’s blood glucose levels. While some diabetes patients have received transplants of islet cells from deceased donors, leading to long-term diabetes control, they must take immunosuppressive drugs to prevent rejection of the transplanted cells.
More recently, researchers have achieved similar success using islet cells derived from stem cells, but patients receiving these cells also require immunosuppressive drugs.
Another option, which could obviate the need for immunosuppressive drugs, is to encapsulate the transplanted cells within a flexible protective device. However, ensuring a reliable oxygen supply for these encapsulated cells has proven to be a challenge.
The MIT team pursued an innovative approach that could potentially provide a perpetual oxygen source by means of water splitting. This involves utilizing a proton-exchange membrane, originally designed for hydrogen generation in fuel cells, within the device. This membrane can split water vapor (abundant in the body) into hydrogen, which harmlessly diffuses away, and oxygen, which is stored and delivered to the islet cells through a thin, oxygen-permeable membrane.
A Batteryless Model that Utilizes Internal Water Vapor to Function
A notable advantage of this approach is that it does not necessitate wires or batteries. Splitting the water vapor requires a low voltage (around 2 volts), generated through resonant inductive coupling. An externally located tuned magnetic coil transmits power to a small, flexible antenna within the device, enabling wireless power transfer. This does require an external coil, which the researchers envision could be worn as a patch on the patient’s skin.
After constructing their device, roughly the size of a U.S. quarter, the researchers tested it in diabetic mice. One group received the device with the oxygen-generating, water-splitting membrane, while the other received a device containing islet cells without supplemental oxygen. The devices were implanted just below the skin, in mice with fully functional immune systems.
The researchers observed that mice implanted with the oxygen-generating device were able to maintain normal blood glucose levels, comparable to healthy animals. In contrast, mice receiving the non-oxygenated device developed hyperglycemia (elevated blood sugar) within approximately two weeks.
Typically, when any type of medical device is implanted, the immune system’s response results in the formation of scar tissue called fibrosis, which can diminish the device’s effectiveness. While this kind of scar tissue did form around the implants in this study, the device’s success in regulating blood glucose levels suggests that insulin could still diffuse out of the device, and glucose could enter it.
This approach could also be applied to deliver cells producing other types of therapeutic proteins required over extended periods. The researchers demonstrated in this study that the device could also sustain cells producing erythropoietin, a protein stimulating red blood cell production.
“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 states. “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 researchers intend to adapt the device for testing in larger animals and humans. For human application, they aim to develop an implant roughly the size of a stick of chewing gum. They also plan to investigate whether the device can remain in the body for extended durations.
“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 remarks.
“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 adds.
“Innovation knows no bounds, and in the realm of healthcare, we’re witnessing the dawn of a new era. With this implant, we’re not just controlling diabetes; we’re reshaping lives.”
- An implantable device could enable injection-free control of diabetes – (https:news.mit.edu/2023/implantable-device-enable-injection-free-control-diabetes-0918)