10 September 2021

Bioengineered pancreas

More than 40 million people worldwide suffer from type 1 diabetes mellitus, an autoimmune disease in which insulin–producing beta cells of the pancreas are destroyed by their own immune system. Currently, new methods of treating type 1 diabetes mellitus are being developed and implemented, including transplantation of beta cells grown from pluripotent stem cells. One of the variations of this approach is macroencapsulation devices (MED) – capsules with insulin-secreting cells. MEDS have a shell that, after transplantation, protects the beta cells inside from attacks from the host body's immune system, while skipping nutrients for the normal functioning of cells. However, MEDS have a number of disadvantages, and scaling such devices for transplantation to patients is very difficult.

A group of researchers from Brigham and Women's Hospital, in collaboration with colleagues from Harvard University and the University of Massachusetts Medical School, have developed MED with improved convection (ceMED), which continuously saturate cells with essential nutrients and improve cell performance, while increasing their survival, glucose sensitivity and ensuring timely insulin secretion.

Existing MEDS work on the principle of diffusion – nutrients pass through the outer membrane of the device, feeding mainly only those cells that are located more superficially. CeMED provides cells with nutrition and oxygen through a continuous flow of fluid, allowing all layers of encapsulated cells to survive and secrete insulin.

The prototype consists of two chambers – the equilibrium chamber (EqC), which collects nutrients from the environment, and the cell chamber (CC), which houses protected beta cells. The EqC is covered with a semi-permeable polytetrafluoroethylene membrane with pores that allow liquid to pass inside. An additional inner membrane covering the CC ensures the transport of nutrients and protects against the attack of the immune system.

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The use of beta cell islands derived from stem cells for the treatment of type 1 diabetes mellitus is currently limited by the risk of rejection. Laboratories around the world are looking for ways to protect cells from an immune response and increase their survival after transplantation. The ceMED design with enhanced convection and a double membrane has the potential to achieve all these goals.

Unlike conventional insulin pumps, ceMED allows cells to secrete insulin if necessary and quickly stop its production as blood glucose levels normalize. In addition, ceMED can work autonomously, without requiring recharging and replacing spent beta cells with new ones. In tests on mouse models of type 1 diabetes mellitus, ceMED increased beta cell survival and insulin secretion and led to normalization of blood glucose levels two days after transplantation.

The group intends to improve the device to increase CC capacity and optimize the beta cell nutrition system.

Article K.Yang et al. A therapeutic convection–enhanced macroencapsulation device for enhancing β cell viability and insulin secretion is published in the journal Proceedings of the National Academy of Sciences.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Building a better bioartificial pancreas.

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