A team of researchers led by diabetes specialists and biomedical engineers from the Washington University School of Medicine in St. Louis and Cornell University have shown that they can use a tiny device to implant insulin secreting cells into diabetic mice. Once implanted, the cells secrete insulin in response to blood sugar, reversing diabetes without the need for drugs to suppress the immune system.
The results will be published in the journal Science Translational Medicine on June 2.
We can take a person’s skin or fat cells, turn them into stem cells, and then grow those stem cells into insulin-producing cells. The problem is that in people with type 1 diabetes, the immune system attacks and destroys these insulin secreting cells. To deliver these cells as therapy, we need devices that house cells that secrete insulin in response to blood sugar and at the same time protect these cells from the immune response. “
Jeffrey R. Millman, PhD, S.This way C.oSolder meInvestigator and Associate Professor of Medicine, Washington University
In previous research, Millman, also associate professor of biomedical engineering, developed and refined a method to produce induced pluripotent stem cells and then to grow these stem cells into insulin secreting beta cells. Millman previously used these beta cells to reverse diabetes in mice, but it wasn’t clear how the insulin secreting cells could be safely implanted in people with diabetes.
“The device, which is about the width of a few strands of hair, is microporous – with openings that are too small for other cells to squeeze into – so that the insulin-producing cells cannot be destroyed by immune cells. that are larger than the openings, “said Millman.” One of the challenges in this scenario is to protect the cells inside the implant without starving them. They still need nutrients and oxygen from the blood to stay alive Zone where the cells inside the device feel accurate and stay healthy and functional, and release insulin in response to blood sugar levels. “
Millman’s lab worked with researchers in the lab of Minglin Ma, PhD, an associate professor of biomedical engineering at Cornell. Ma has worked to develop biomaterials that can help safely implant beta cells in animals, and ultimately, people with type 1 diabetes.
In the past few years several implants have been tried with varying degrees of success. For this study, Ma, the other co-leader of the study, and his colleagues developed a so-called nanofiber-integrated cell encapsulation device (NICE). They filled the implants with insulin-secreting beta cells made from stem cells and then implanted the devices in the abdomen of mice with diabetes.
“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 stalling it and rendering it ineffective,” Ma said. “The implants floated freely inside the animals, and when we removed them after about six months, the insulin-secreting cells in the implants were still working. And above all, it is a very robust and safe device. “
The cells in the implants continued to secrete insulin and controlled blood sugar levels in the mice for up to 200 days. And these cells continued to function even though the mice were not treated with anything to suppress their immune systems.
“We’d rather not have to use drugs to suppress someone’s immune system because that would make the patient susceptible to infection,” said Millman. “The device we used in these experiments protected the implanted cells from the mice’s immune system, and we believe similar devices could work the same way in people with insulin-dependent diabetes.”
Millman and Ma are reluctant to predict how long it would be before such a strategy could be applied clinically, but they plan to continue working towards that goal.
Source:
Washington University in St. Louis
Journal reference:
Wang, X, et al. (2021) A nanofiber encapsulation device for the safe delivery of insulin-producing cells for the treatment of type 1 diabetes. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb4601.
