Xenotransplantation as a therapy for type 1 diabetes
Type 1 diabetes is caused by an autoimmune reaction which ultimately leads to the destruction of the insulin-producing cells in the pancreas, and usually becomes manifest during adolescence. Thereafter, insulin must be administered by regular insulin injections. Since insulin therapy cannot reproduce the complex pattern of physiologically controlled insulin secretion, patients are at risk of hypoglycemia and many patients develop severe vascular complications such as myocardial infarction or stroke.
Transplantation of a healthy pancreas or pancreatic beta cells that synthesize insulin may represent the best treatment option. Unfortunately, the availability of donor organs falls far short of requirements. Over the course of the last several years, fewer than 200 pancreas transplantations have been carried out. “Pigs represent a possible alternative source, because glucose metabolism in this species is very similar to that in human beings,” Professor Seissler points out.
Pig insulin differs from its counterpart in humans at only a single amino acid, and has been used successfully in the treatment of diabetic patients for decades. However, pig cells inevitably provoke an immune reaction leading to the destruction of the transplanted tissue. One way of avoiding this difficulty is to encapsulate the foreign tissue in a biologically inert material that is permeable to insulin but not to cells of the immune system. However, the drawback of this approach is the restricted supply of oxygen and essential nutrients to the transplanted cells, thereby reducing its lifespan.
Wolf and his team chose a different route. For the first time they generated genetically modified pigs that express the protein LEA29Y specifically in beta cells. LEA29Y effectively inhibits the activation of a class of immune cells that are required to initiate a rejection reaction. The researchers then transplanted these cells into a diabetic mouse strain that has a humanized immune system. Seissler’s group showed that these mice were able to restore glucose metabolism and were protected form human-anti-pig rejection. As Wolf is quick to point out, “It is not yet clear whether this will also work in humans. However, we will now attempt to validate the effects of this very promising approach using beta-cells expressing immune modulators in other transplantation models.” suwe
„Xenografted Islet Cell Clusters From INSLEA29Y Transgenic Pigs Rescue Diabetes and Prevent Immune Rejection in Humanized Mice”
Nikolai Klymiuk, Lelia van Buerck, Andrea Bahr, Monika Offers, Barbara Kessler, Annegret Wuensch, Mayuko Kurome, Michael Thormann, Katharina Lochner, Hiroshi Nagashima, Nadja Herbach, Rudiger Wanke, Jochen Seissler, and Eckhard Wolf
Diabetes online, 20. April 2012
Prof. Dr. Eckhard Wolf
Chair of Molecular Animal Genetics and Biotechnology
Genzentrum, LMU Munich
Prof. Dr. Jochen Seissler
Medizinische Klinik und Poliklinik IV – Campus Innenstadt