In type 1 diabetes, a lifelong disease that requires patients to inject themselves with insulin several times a day, the problem starts with dysfunctional cells in a nook of the pancreas called the islets of Langerhans.
The cells, called beta cells, produce insulin in response to glucose, or sugar, in the bloodstream. In type 1 diabetes, the body mistakes these cells for an immune threat and kills them off, leaving patients with no natural supply of insulin.
Because the tiny patch of beta cells plays such a vital role in keeping the body running, researchers have sought a way to introduce new working beta cells into patients. But there are major challenges.
One significant development came a few years ago when researchers put human pancreatic stem cells into mice. Within a few weeks, the mice were processing glucose normally.
This week, Harvard researchers made what many are hailing as a major improvement to that system. They successfully coaxed pancreatic stem cells to specialize as beta cells in the laboratory. When these cells were then implanted in mice, the animals went from having high blood sugar levels to responding normally to glucose in a matter of days.
“If you didn’t tell me anything and sent me these cells, I would say, ‘These are human islet cells,’” said Dr. Jose Oberholzer, a transplant surgeon and endocrinologist at the University of Illinois at Chicago who has followed the work closely.
A Small Step with Big Implications
The advance may sound minor, but it’s the kind of improvement that makes a big difference for patients.
The pancreatic stem cells used in the earlier research carry a substantial risk of cancer precisely because they’re still growing and changing when they are transplanted. The researchers have since begun putting the cells into credit card-sized packets before implanting them in order to wall off the risk of cancer. Fully specialized cells don’t introduce the same risk.
Beta cells made in the lab also offer a second benefit: They can provide a useful research model of diabetes. That will speed drug development. Harvard researchers are already working on cultivating beta cells from patients with diabetes, which would let them watch the disease at work on the cellular level, said Felicia Pagliuca, one of the paper’s authors.
Pagliuca is a postdoctoral fellow in senior study author Douglas Melton’s lab in the Department of Stem Cells and Regenerative Biology at Harvard. Melton’s two children have type 1 diabetes, and the work is so personal to him that experts refer to “Doug’s work” and “Doug’s cells.” (Healthline was unable to reach Melton for comment.)
The Harvard lab obtained the cells using a method that could be scaled up to produce the massive quantities of beta cells that would be required to treat the two million Americans who suffer from type 1 diabetes. Stem cells are finicky, and mass production still needs to be perfected.
“One of the things that we’ve always had in the back of our minds is that we want this to be not only a scientific advance, but also a medical advance for patients,” said Pagliuca.
Protecting Precious Beta Cells
Of course, there are two parts to giving patients with diabetes, whose immune systems have destroyed their own beta cells, a way to control insulin without injections. They need both the new cells and a way to safeguard those cells.
There is work happening in parallel to the research at Harvard to create tiny packets to protect the cells without triggering an immune response. The wraps are the consistency of Jell-O.
“You want to wrap these cells in a material that allows sugar and nutrients and insulin to go in and out but protects the cells from the immune system,” said Daniel Anderson, a professor of applied biology at the Massachusetts Institute of Technology.
There’s a second approach to protecting new beta cells, too: immunosuppressant drugs. Those drugs have allowed doctors to experiment with transplanting islets of Langerhans from organ donors. Transplants, however, remain experimental and don’t offer the same pristine cells.
Oberholzer now does about 10 islet transplants a year on patients who are among the roughly 50,000 whose disease rages out of control even after standard treatment. Even if islet transplants were to cease being experimental, Oberholzer said, the number of transplants would top out at 150 per year because there just aren’t enough donors.
“I can do transplants and they do work, but I can’t do enough. Now Doug’s work says if we do a few more tests and show that these cells are safe, you can go and do as many transplants as you want,” he said.
Without seeing the sickest diabetes patients day in and day out, Oberholzer said, it might be “difficult to grasp” what it would mean to be able to offer patients more than a difficult, imperfect treatment like insulin injections and instead something much closer to a cure.