Brigham bioengineers have developed a convection-enhanced macroencapsulation gadget that provides the potential of sooner and more practical remedy for individuals with kind 1 diabetes.
More than 40 million individuals worldwide are affected with kind 1 diabetes (T1D) mellitus, an autoimmune illness by which insulin producing β-cells within the pancreas are destroyed by the immune system. Today, there are a number of new and rising remedy strategies for kind 1 diabetes, together with macroencapsulation gadgets (MEDs) — compartments designed to accommodate and shield insulin-secreting cells. Like a go well with of armor round a knight, the MEDs shield the cells inside it from assault (from the host immune system) whereas permitting vitamins out and in in order that the cells can proceed to outlive. But MEDs have a number of limitations and scaling up such gadgets for use in people has been difficult. A workforce of researchers from Brigham and Women’s Hospital in collaboration with colleagues at Harvard University and the University of Massachusetts Medical School has designed a convection-enhanced MED (ceMED), which may constantly bathe cells within the vitamins they want and enhance cell loading capability, whereas growing cell survival, glucose sensitivity and well timed insulin secretion. In preclinical fashions, the ceMED quickly responded to blood sugar ranges inside two days of being implanted. Results are printed in The Proceedings of the National Academy of Sciences.
“Thanks to recent advances, we’re getting closer and closer to having an unlimited source of β-like cells that can respond to glucose by secreting insulin, but the next challenge is getting those cells into the body in a way that’s minimally invasive and will have longevity with maximal function,” mentioned corresponding creator Jeff Karp, PhD, principal investigator and Distinguished Chair in Clinical Anesthesiology, Perioperative and Pain Medicine. “Our device demonstrated enhanced cell viability and minimal delay following transplantation. It’s a strong preclinical proof of concept for this system.”
Current MEDs are diffusion dependent — vitamins diffuse throughout the outer membrane of the gadget and solely a variety of cells might obtain vitamins and oxygen and, in flip, secrete insulin. The ceMED was designed to offer convective vitamins by way of a steady movement of fluid to the encapsulated cells, permitting a number of layers of cells to develop and survive. The workforce’s prototype options two chambers — an equilibrium chamber (EqC) that collects vitamins from the environment and a cell chamber (CC) that homes the protected cells. The EqC is enclosed in polytetrafluoroethylene — a semi-permeable membrane with pores that permit fluids in. An extra internal membrane surrounding the CC selectively permits for nutrient transport and protects towards immune responses. Perfused liquids movement by way of a porous hole fiber reaching the CC at a related focus of vitamins because the tissue surrounding the implant. The hole fiber permits insulin and glucose to freely move however doesn’t permit key immune molecules in that would assault the encapsulated cells.
“The application of stem cell-derived islets to treat autoimmune or Type 1 diabetes has now moved to the point of finding a method to protect the cells from immune rejection and maximizing their survival and function following transplantation,” mentioned co-author Doug Melton, PhD, of the Department of Stem Cell and Regenerative Biology on the Harvard Stem Cell Institute. “Convection-enhanced macroencapsulation may well be a viable approach to achieve all of these goals.”
The gadget affords many benefits over standard insulin pumps and permits cells to secrete insulin on demand and rapidly cease secreting insulin as blood glucose ranges decline. In rodent fashions of kind 1 diabetes, the ceMED enhanced the survival and insulin secretions of cells and commenced to lower blood glucose degree as early as two days post-transplantation.
“The ceMED device has the potential to be an autonomous system that would not require constant refilling and replacement of insulin cartridges,” mentioned lead creator Kisuk Yang, PhD, a former postdoctoral fellow within the Karp Lab and now school on the Division of Bioengineering at Incheon National University in South Korea.
“Due to its responsiveness, this device and novel flow-enhanced approach could be particularly useful for ‘brittle’ diabetics, people whose diabetes results in unpredictable swings in blood sugar levels,” added Eoin O’Cearbhaill, PhD (now at University College Dublin, Ireland), a co-author who helped develop this idea whereas working as a postdoctoral fellow within the Karp Lab. The workforce notes future instructions that may have to be pursued to convey the gadget to the clinic, together with scaling up cell loading capability and optimizing the perfused movement system for human use.
“Overall, these results highlight significant advantages of ceMED over existing diffusion-based devices including improved cell survival, reduced fibrous encapsulation that can compromise functionality over time, and quicker on and off rates for insulin secretion,” mentioned Karp. “This approach has the potential to enhance the success of β cell replacement therapies to help many T1D patients and their families manage this challenging disease.”
Reference: “A Therapeutic Convection Enhanced Macroencapsulation Device for Enhancing β Cell Viability and Insulin Secretion” by Yang Ok et al., 6 September 2021, Proceedings of the National Academy of Sciences.
Funding: This work was supported by the Juvenile Diabetes Research Foundation (3-SRA-2013-282), and the National Institutes of Health (R01 grant HL095722 and U01DK104218), and the Incheon National University Research Grant in 2021.