More than 40 million people worldwide have type 1 diabetes (T1D). It is an autoimmune disease in which the insulin-producing beta cells of the pancreas are destroyed by the immune system. Today, there are several new new treatments for type 1 diabetes, including macroencapsulation devices (MEDs), compartments designed to contain and protect insulin-secreting cells. Like armor around a knight, MED protects the cells in it from attack (from the host’s immune system) while allowing nutrients to move in and out so that the cells can survive. However, MED has some limitations and it has been difficult to scale up such devices for human use. In collaboration with colleagues at Harvard University and the University of Massachusetts School of Medicine, a team of researchers at Brigham and Women’s Hospital have designed a convection-enhancing MED (ceMED) that can continuously soak cells with the nutrients they need to improve cell load capacity. bottom. While increasing cell viability, glucose sensitivity and timely insulin secretion. In the preclinical model, ceMED responded rapidly to blood glucose levels within 2 days after transplantation.The results are published in Minutes of the National Academy of Sciences..
“Thanks to recent advances, we are getting closer and closer to having an unlimited source of things like beta. cell Can react to grapes by secreting InsulinHowever, the next challenge is to bring these cells into the body in a minimally invasive, life-saving manner, “said the corresponding author, Principal Investigator of Clinical Anesthesia, Perioperative and Pain. Dr. Jeff Carp, also and prominent chairman, said. Medicine. “Our device has shown improved cell viability and minimal delay after transplantation. This is a powerful preclinical proof of concept for this system.”
Today’s MED relies on diffusion. Nutrients diffuse throughout the outer membrane of the device, and only many cells can receive nutrients and oxygen and secrete insulin. ceMED is designed to provide convective nutrients through a continuous flow of fluid into encapsulated cells, allowing multiple layers of cells to grow and survive. The team’s prototype has two chambers: an equilibrium chamber (EqC) that collects nutrients from the surroundings and a cell chamber (CC) that houses protected cells. EqC is surrounded by polytetrafluoroethylene (a semipermeable membrane with pores for liquids). The additional endometrium surrounding the CC selectively allows the transport of nutrients and protects them from the immune response. The perfused liquid flows through the porous hollow fibers and reaches CC with the same concentration of nutrients as the tissue surrounding the implant. Hollow fibers allow insulin and glucose to pass freely, but do not allow important immune molecules that can attack the encapsulated cells.
“The application of stem cell-derived islets to treat autoimmunity or type 1 diabetes has led to finding ways to protect cells from immune rejection and maximize survival and function after transplantation,” co-authored. Says Doug Melton. PhD in Stem Cell and Regenerative Biology from Harvard Institute for Stem Cell Research. “Convection-enhanced macroencapsulation could be a viable approach to achieving all these goals.”
This device offers many advantages over traditional insulin pumps, allowing cells to secrete insulin on demand and quickly stop insulin secretion when blood sugar levels drop. In a rodent model of type 1 diabetes, ceMED enhanced cell survival and insulin secretion and began to lower blood glucose levels two days after transplantation.
“The ceMED device could be an autonomous system that does not require regular refilling or replacement of Incheon cartridges,” said Dr. Kisuk Yang, a former postdoctoral fellow at Karp Lab and now a faculty member of the Division. increase. He holds a PhD in biotechnology from Incheon National University in South Korea.
“Because of its responsiveness, this device and the new flow-enhancing approach can be especially useful for’fragile’diabetics, where diabetes causes unpredictable fluctuations in blood glucose levels,” added Dr. Eoin O’Cearbhaill. (Currently in Dublin, University College Dublin, Ireland), a co-author who helped develop this concept while working as a postdoc at Karp Lab. The team will focus on future directions that need to be pursued to bring the device to the clinic, such as scaling up cell loading capacity and optimizing the perfusion system for human use.
“Overall, these results highlight the important benefits of ceMED over existing diffusion-based devices, including improvements. Cell survival, Decreased fibrotic encapsulation, which can be impaired over time, and increased insulin secretion on / off rates, “Carp said. disease. ”
Therapeutic convection-enhancing macroencapsulation device for enhancing beta-cell viability and insulin secretion, Minutes of the National Academy of Sciences (2021). DOI: 10.1073 / pnas.2101258118
Brigham and Women’s Hospital
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