Diabetes specialists and biomedical engineers from Washington University School of Medicine in St. Louis and Cornell University have shown that they can implant insulin-secreting cells into diabetic rats using a tiny device.
The cells produce insulin in accordance to blood sugar after being implanted, curing diabetes without the need of immune-suppressing medicines. The findings were reported in Science Translational Medicine on June 2nd.
“We can take a person’s skin or fat cells, make them into stem cells and then grow those stem cells into insulin-secreting cells,” said Jeffrey R. Millman, Ph.D., an associate professor of medicine at Washington University and one of the study’s co-senior investigators. “The problem is that in people with Type 1 diabetes, the immune system attacks those insulin-secreting cells and destroys them. To deliver those cells as a therapy, we need devices to house cells that secrete insulin in response to blood sugar, while also protecting those cells from the immune response.”
Millman, who is also an associate professor of biomedical engineering, previously established and refined a method for producing induced pluripotent stem cells and then growing them into insulin-secreting beta cells. Millman had previously utilized beta cells to treat diabetes in animals, but it was unclear how the insulin-secreting cells could be safely implanted into diabetic people.
“The device, which is about the width of a few strands of hair, is micro-porous—with openings too small for other cells to squeeze into—so the insulin-secreting cells consequently can’t be destroyed by immune cells, which are larger than the openings,” said Millman. “One of challenges in this scenario is to protect the cells inside of the implant without starving them. They still need nutrients and oxygen from the blood to stay alive. With this device, we seem to have made something in what you might call a Goldilocks zone, where the cells could feel just right inside the device and remain healthy and functional, releasing insulin in response to blood sugar levels.”
Millman’s lab collaborated with Minglin Ma, Ph.D., an associate professor of biomedical engineering at Cornell, and his colleagues. Ma has been developing biomaterials that can be used to safely transplant beta cells into animals and, eventually, people with Type 1 diabetes.
In recent years, a number of implants have been tested, with varied degrees of effectiveness. For this study,
Ma and his colleagues created a nanofiber-integrated cell encapsulation (NICE) technology. They then inserted the implants into the abdomens of diabetic mice, where they were filled with insulin-secreting beta cells made from stem cells.
“The combined structural, mechanical and chemical properties of the device we used kept other cells in the mice from completely isolating the implant and, essentially, choking it off and making it ineffective,” Ma said. “The implants floated freely inside the animals, and when we removed them after about six months, the insulin-secreting cells inside the implants still were functioning. And importantly, it is a very robust and safe device.”
For up to 200 days, the cells in the implants continued to release insulin and manage blood sugar in the animals.
Despite the fact that the mice were not given anything to dampen their immune systems, the cells continued to operate.
“We’d rather not have to suppress someone’s immune system with drugs, because that would make the patient vulnerable to infections,” Millman said. “The device we used in these experiments protected the implanted cells from the mice’s immune systems, and we believe similar devices could work the same way in people with insulin-dependent diabetes.”