A device implanted into mice, coupled with a ground-breaking cell design, is a breakthrough toward a cure for Type 1 diabetes by allowing insulin-producing cells to function successfully in people with diabetes.
“I think it’s really cool,” Dr. Jeffrey R. Millman, with the Washington University School of Medicine, said about significant progress on curing diabetes announced by a team of researchers last week. “I’ll be honest, I was shocked at how well the system, the encapsulation system, worked here. We had tried to solve this many times. We had developed a lot of these devices. This was a really hard problem.”
The specific problem successfully solved was developing a device that allows the insulin produced by stem cells to enter the bloodstream while, at the same time blocking the immune system from killing those same cells.
“The material [in the device] has micro-pores that are so small that the immune cells can’t come in and kill the cells you want to have function,” Millman said, “but they’re large enough for insulin to come out, and sugar, or oxygen, can come in so you give the cells food and allow them to breathe so they survive and also allow them to deliver insulin to the bloodstream of the recipient.”
The insulin-producing stem cells, called islet cells, require protection from the immune system because of traits in the immune system unique to people with Type 1 diabetes,” Millman said.
“Type 1 diabetes is more problematic than in other situations because we have to deal with the immune system being too strong,” Millman said. “In type 1 diabetes it’s what called an autoimmune attack. Basically, the immune system attacks and destroys the patient’s cells that make insulin.”
Millman said that even stem cells generated by the person receiving them are prone to attack by the immune system if that person has Type 1 diabetes. Such an attack by the immune system is the initial cause of diabetes to start with,” Millman said.
While test subjects have been receiving islet cell transplants in testing to develop a cure for diabetes for many years, transplants have not proven a long-term solution mainly because of attacks by the immune system. And, while those subjects take medication to suppress their immune system, those come with their own set of problems. Some scientists even suspect that the harsh drug regime itself might be harming or destroying the delicate islet cells.
“The immune response makes it harder for us,” Millman said. “But we think the physical barrier is a good approach to solve this.”
The device is not the first breakthrough in research conducted by Millman and others on his team in their efforts to cure Type 1 diabetes. In February 2020, Millman’s team announced they had developed a procedure to create insulin-producing stem cells and that those cells were functioning successfully in mice.
“That is our claim to fame, if you will,” Millman said. “We figured out how to effectively transform stem cells to be insulin-producing cells. And, since then, we’ve made a lot of improvements in the process to make it more efficient.”
This solved a supply issue of islet cells for transplantation. Test subjects who have received islet cell transplants have received cells donated from cadaver pancreases, of which, as with organ donations, there is a very short supply.
“Instead of receiving insulin-producing islet cells from donors, it would be these cells,” Millman said about the technology that is now with a biotech firm for further development. “That’s a substantial jump right there to go from relying on deceased donors for these cells to having a renewable supply of these cells. Now, we would be able to generate million or billions of these cells in even a fairly modest laboratory.”
Successfully developing insulin-producing stem cells, however, was not the answer to the riddle of Type 1 diabetes. Researchers who so far have spent several years and more than $1 million in public and private research money, were aware of that even back then.
“We knew the next frontier in the quest for a cure was to be able to have the islet cells function in Type 1 diabetics without having to be immunosuppressed,” Millman said. “Now, on probably the tenth attempt and maybe the fifth collaborator we worked with, we developed a device that does that in mice and in dogs. The solution was quite elegant, and quite robust, in terms of how well it worked.”
While Millman and his team are pleased with the results of their work, Millman is cautious about the many, many things that still need to happen for the technology to function as successfully in people, as it does in mice.
“This is a situation where we’re not at the beginning,” Millman said, while declining to speculate on how long it might take before his work is applicable in humans. “This is not step one. We have worked out many of the problems in terms of translating the approaches into something that could actually go into people who can benefit from it. There is still a lot of work to be done, however, to make sure this works well in a creature that is larger than a 30-gram mouse. That’s probably the biggest challenge on the horizon right now.”