Using an innovative hydrogel that promotes the survival of insulin-producing cells grafted into the body, scientists have successfully regulated blood glucose levels in diabetic mice. This experimental breakthrough, which outperforms conventional transplantation methods, paves the way for the development of a bioartificial pancreas that could eliminate the need for insulin injections. These results, obtained as part of the European VANGUARD project, are published in the journal
Trends in Biotechnology.
Clusters of insulin-producing islet cells (in red) housed within the hydrogel designed by the UNIGE and HUG team. Blue dots represent cell nuclei.
Β© Berishvili Lab, University of Geneva
Type 1 diabetes occurs when the immune system destroys the insulin-producing Ξ² cells of the pancreas, leading to a chronic dysregulation of blood sugar levels. To compensate for this deficiency, affected individuals must inject insulin daily for life.
Transplantation of pancreatic islets β small groups of cells that produce insulin and other hormones β can temporarily restore glycemic balance and eliminate the need for artificial insulin. However, this approach remains limited by the scarcity of donations and the high risk of rejection. Additionally, when pancreatic islets are implanted in the liver β the usual transplantation site β they face inflammation, loss of their natural support matrix, and insufficient blood supply, all factors that compromise their survival.
This experimental proof represents a decisive step toward the development of a functional artificial pancreas.
A team led by Ekaterine Berishvili, professor in the Department of Surgery and the Diabetes Center of the UNIGE Faculty of Medicine, and head of the Cell Isolation and Transplantation Laboratory at the HUG Transplantation Service, has developed an innovative hydrogel called Amniogel that overcomes these obstacles.
Derived from the human amniotic membrane β the innermost layer of the membranes surrounding the fetus, easily collected from the placenta after birth β it restores survival signals lost during the isolation of pancreatic islets and allows a microvascular network to self-assemble within the structure before transplantation. Once implanted, this preformed network connects to the host's blood circulation, promoting long-term graft function. In laboratory tests, the gel also slows the migration of cytotoxic immune cells, suggesting it could help protect the graft in the early period following transplantation.
Normal blood glucose for at least 100 days
"This gel creates a protective environment, similar to that of the body, into which we incorporate pancreatic islets as well as vessel-forming cells. Before transplantation, these cells self-organize into a microvessel network surrounding the islets, so the graft arrives already vascularized," explains Ekaterine Berishvili. Successfully transplanted into diabetic mice, this structure β thin disc-shaped grafts about 0.35 inches (9 mm) in diameter β maintained normal blood glucose for at least 100 days, the entire duration of monitoring, outperforming both islets transplanted alone and structures without artificial vasculature. Amniogel is also produced according to GMP (Good Manufacturing Practice) pharmaceutical standards, an essential requirement for future clinical application.
Close to clinical application
"This experimental proof represents a decisive step toward the development of a functional artificial pancreas," the researcher rejoices. "The next step, to consider clinical application, will be to produce larger grafts β or a greater number of them β to meet the needs for use in humans." Additionally, Amniogel could be used to house many other types of cells, opening the door to cell transplantation therapies beyond diabetes.