Diabetes (AG Seißler)
Research Group Xenotransplantation and Cell Therapy
Type 1 diabetes (T1D) is caused by complete destruction of insulin-producing pancreatic islet cell leading to life-long dependence on daily insulin injections. It has been shown that transplantation of pancreas or islolated islets can cure the disease. However, this aproach is limted by the requirement of large numbers of high quality islets and the shortage of organ donors. Porcine islets are a promising alternative cell source, but translation of pig islet transplantation into clinical practice is hampered by the strong xenoreactive rejection.
Previous work
Our research group has shown for the first time that it is possible to cure type 1 diabetes by the transplantation of porcine islets with specific genetic modifications.
Pig islets overeexpressing the immunomodulatory molecules LEA29Y were protected form human immune cell attacks in NOD-scid-IL2γnull (NSG) mice after transfer of human PBMCs and in NSG mice carrying a stable human immune system (hCD34+ cell transfer model).
Aims of research
- To identify the best transgene-knock-out combinations needed to achieve long-term acceptance against grafted porcine islets with minimized systemic immunosuppression
- To identify novel immunomodulatory therapies that induce active tolerance against porcine islets and can be applied in humans
- To provide preclinical data to advance xenotransplantation to a position to perform clinical pilot studies in patients with T1D
