A bioartificial pancreas could be the solution for diabetic patients

Insulin is the hormone that helps glucose get into cells for energy. Without insulin, there is excess glucose left in the blood. In some people, mainly children, adolescents and young adults, the pancreas does not produce much insulin and type 1 diabetes develops. For these patients, scientists working at Brigham and Women’s Hospital, Harvard Medical School’s second-largest teaching hospital in the United States, have developed an improved version of an artificial pancreas.

The pancreas is located under and behind the stomach in humans. Insulin is needed to mobilize blood sugar (glucose) in cells. Glucose is stored in cells and is then used for energy. With type 1 diabetes, beta cells produce little or no insulin.

As symptoms of the disorder, the person may be very thirsty, hungry more often, feel tired all the time, have blurred vision, feel numbness or tingling in their feet, lose weight despite increased appetite, and often urinate more frequently.

Scientists at Harvard University Hospital were able to develop an improved macroencapsulation device by convection which offers the possibility of becoming a faster and more effective treatment for people with type 1 diabetes.

Over 40 million people worldwide have type 1 diabetes. It is an autoimmune disease in which the insulin-producing beta cells in the pancreas are destroyed by the immune system. Currently there are several new and emerging treatment methods for type 1 diabetes, such as macroencapsulation devices, which consist of compartments designed to house and protect insulin-secreting cells.

As if it were an armor of medieval knights, different scientific groups have worked on different models of bioartificial pancreas to protect cells against attacks from the immune system from the same host. They also sought to have the device allow the entry and exit of nutrients so that the cells could continue to survive.

But this type of development has had several limitations and the transfer for its use in humans has been a challenge. The team of researchers from Brigham and Women’s Hospital, in collaboration with colleagues from other sectors of the Harvard University and University of Massachusetts School of Medicine, designed an improved macroencapsulation by convection, It can continuously bathe cells with the nutrients they need and improve cell carrying capacity, while increasing cell survival, glucose sensitivity and timely insulin secretion.

At preclinical animal models, the device responded quickly to blood sugar levels within two days of implantation. The results are published in Proceedings of the National Academy of Sciences. “Thanks to recent advancements, we are getting closer and closer to an unlimited source of beta cells capable of responding to glucose by secreting insulin, but the next challenge is to introduce these cells into the body in a minimally invasive and to have longevity. with maximum function, ”said scientist Jeff Karp, MD, principal investigator and professor emeritus of clinical anesthesiology, perioperative medicine and pain medicine.

“Our device demonstrated greater cell viability and minimal delay after transplantation. This is a strong preclinical proof of concept for this system, ”he added. Similar devices today are diffusion dependent: nutrients diffuse through the outer membrane and only a certain number of cells can receive nutrients and oxygen and, in turn, secrete insulin.

The one now designed in the United States seeks to deliver nutrients by convection through a continuous flow of fluid to the encapsulated cells. This allows multiple layers of cells to grow and survive. The team’s prototype has two chambers: a balance chamber that collects nutrients from the environment and a cell chamber that houses protected cells. The first chamber is enclosed in polytetrafluoroethylene, a semi-permeable membrane with pores that allow the entry of fluids. An additional inner membrane surrounding the second chamber allows selective transport of nutrients and protects against immune responses.

The infused fluids flow through a porous hollow fiber that reaches the cell chamber with a concentration of nutrients similar to that of the tissue surrounding the implant. Fiber allows insulin and glucose to pass freely, but does not allow the entry of molecules from the immune system that could attack the encapsulated cells.

“The application of islets derived from stem cells for the treatment of type 1 or autoimmune diabetes has now gone to the point of finding a method to protect cells from immune rejection and maximize their survival and function after transplantation,” said co-author Doug. Melton, who is in the Department of Stem Cells and Regenerative Biology at Harvard Stem Cell Institute. “Convection-enhanced macroencapsulation may be a viable approach to achieve all of these goals.”

The device offers many advantages over conventional insulin pumps and allows cells to secrete insulin on demand and shut down quickly when blood sugar drops. In rodent models with type 1 diabetes, the device improved survival and insulin secretion by cells and began to lower blood sugar as early as two days after transplantation.

“The device has the potential to be a stand-alone system that would not require constant refilling and replacement of insulin cartridges,” said lead author Dr Kisuk Yang, a former postdoctoral fellow at the Karp Laboratory and now a professor in the division of bioengineering at Incheon National University in South Korea.

For its responsiveness, This device and the new improved flow method could be particularly useful for people with labile diabetes – that is, people whose diabetes causes unpredictable fluctuations in blood sugar levels, said Dr Eoin O’Cearbhaill ( now at University College of Dublin, Ireland), another of the researchers who helped develop the device while working as a postdoctoral fellow in Karp’s lab. The team indicates future directions for bringing the device to the clinic, including increasing cell loading capacity and optimizing the perfused flow system for human use.

“In fgeneral, These results highlight significant advantages over existing systems based on diffusion, including improved cell survival, reduced fibrous encapsulation which can compromise functionality over time, and faster activation and deactivation rates of insulin secretion, ”said Karp. “This approach has the potential to improve the success of beta cell replacement therapies in helping many patients with type 1 diabetes and their families manage this difficult disease,” he said.

The work was supported by the Juvenile Diabetes Research Foundation and the National Institutes of Health, and a research grant from National University of Incheon, South Korea, in 2021.

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