Type I diabetes mellitus (T1D) is an autoimmune disease that results in the permanent loss of insulin-producing beta cells in the pancreas. In a new study, researchers from the University of Tokyo developed a novel device for long-term transplantation of iPSC-derived human pancreatic beta cells.
T1D occurs when autoimmune antibodies destroy pancreatic beta cells, which are responsible for producing insulin. Insulin regulates blood sugar levels, and in the absence of it, high blood sugar levels slowly raise the kidneys, eyes, and peripheral nerves. As the body loses the ability to produce insulin over time, the current mainstay of treatment for T1D is injecting insulin. An exciting research undertaking over the past decade has been to find ways to replace lost beta cells with cell therapy.
“Cell therapy is an exciting but challenging approach to treating type I diabetes mellitus,” says lead author of the study, Professor Shoji Takeuchi. “The challenge arises from the difficulty of producing large quantities of human beta cells in a dish and, above all, achieving safe and effective transplantation. In this study, we wanted to develop a new construct that enables successful transplantation of beta cells onto long term. “
To achieve their goal, the researchers developed a lotus root-shaped cell-encapsulated construct (LENCON) and packaged it with human iPSC-derived pancreatic beta cells, which are an unlimited source of cells and allow any number of beta cells to be produced. The need for such an encapsulation technique arises from the fact that immune cells of the recipient could destroy the newly transplanted cells. To prevent this from happening, the researchers constructed the millimeter-thick LENCON transplant. It has already been shown that the millimeter-thick graft diameters weaken the body’s immune response to a foreign body. At a millimeter thick, oxygen and nutrients could not be delivered to the center of the cells, but using a lotus root shape the cells were only placed near the edge of the graft where oxygen and nutrients could diffuse sufficiently, creating an environment in which the cells could survive even in a millimeter-thick graft.
After the development of the LENCON, the question arose whether it could effectively control blood sugar levels in the long term without triggering an immune response. To answer this question, the researchers transplanted the construct into immunodeficient and immunocompetent diabetic mice. The former helped study the effectiveness of the graft in controlling blood sugar levels without an immune response, while the latter addressed both goals. The researchers found that LENCON was able to maintain normal blood sugar levels for more than 180 days in the former mice and could be removed without adhesion in the latter mice after more than a year of transplantation.
“These are remarkable results that show how LENCON can be used successfully and safely in type I diabetes mellitus. Our results suggest that LENCON could offer a novel option for cell therapy in type I diabetes mellitus,” says the first author of the study Dr. Fumisato Ozawa.
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Materials provided by Institute of Industrial Science, University of Tokyo. Note: the content can be edited by style and length.
