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.
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
Selected Publications Xenotransplantation and Cell Therapy
Fischer A, Manske K, Seissler J, Wohlleber D, Simm N, Wolf-van Buerck L, Knolle P, Schnieke A, Fischer K. (2020). Cytokine-inducible promoters to drive dynamic transgene expression: The "Smart Graft" strategy. Xenotransplantation 27(6):e12634.
Carvalho Oliveira M, Valdivia E, Verboom M, Yuzefovych Y, Sake H, Pogozhykh O, Niemann H, Schwinzer R, Petersen B, Seissler J, Blasczyk R, Figueiredo C. (2020). Generating low immunogenic pig pancreatic islet cell clusters for xenotransplantation. J Cell Mol Med. 24:5070-5081.
Wolf-van Buerck, Schuster M, Oduncu FS, Baehr A, Mayr T, Guethoff S, Abicht J, Reichart B, Klymiuk N, Wolf E, Seissler J. (2017). LEA29Y expression in transgenic neonatal porcine islet-like cluster promotes long-lasting xenograft survival in humanized mice without immunosuppressive therapy. Sci Rep 7(1):3572.
Wolf-van Buerck L, Schuster M, Baehr A, Mayr T, Guethoff S, Abicht J, Reichart B, Nam-Apostolopoulos YC, Klymiuk N, Wolf E, Seissler J. (2015). Engraftment and reversal of diabetes after intramuscular transplantation of neonatal porcine islet-like clusters. Xenotransplantation 22:443-450.
Arndt B, Witkowski L, Ellwart J, Seissler J. (2015). CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice. J Leukoc Biol 97:111-120.
Klymiuk N*; van Bürck L*, Bähr A, Offers M, Kessler B, Wuensch A, Kurome M, Thormann M, Lochner K, Nagashima H, Herbach N, Wanke R, Seissler J#, Wolf E#. (2012). Xenografted islet-cell-clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection in humanized mice. Diabetes 61:1527-1532.
Research Group Type 2 Diabetes
Our mission is to improve the health of individuals with prediabetes and diabetes by the identification of specific diabetes subtypes and the establishment of novel individualized therapies.
In the population-based KORA-study and the prediction, prevention and subclassification of diabetes study (PPS-Diab) we identified specific patterns of serum biomarkers, metabolites and genetic markers associated with progression to type 2 diabetes and cardiovascular complications.
We characterised the clinical and metabolic profiles of persons at increased risk for diabetes and we have identified a subgroup of high risk patients who display no signs of metabolic syndrome.
Aims of research
- To analyse the pathophysiological mechanisms involved in the development of different subtypes of type 2 diabetes
- To characterise the link between genetic, metabolic and environmental factors leading to deterioration of beta-cell function
- To screen for predictive biomarkers of prediabetes using novel omic-technologies
- To test new interventions strategies
Selected Publications Clinical Studies
Rottenkolber M, Gar C, Then C, Wanger L, Sacco V, Banning F, Potzel AL, Kern-Matschilles S, Nevinny-Stickel-Hinzpeter C, Grallert H, Hesse N, Seissler J, Lechner A. (2021). A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome. Clin Endocrinol Metab. 2021 Jan 30:dgab057. doi: 10.1210/clinem/dgab057.
Gar C, Haschka SJ, Kern-Matschilles S, Rauch B, Sacco V, Prehn C, Adamski J, Seissler J, Wewer Albrechtsen NJ, Holst JJ, Lechner A. (2021). The liver-alpha cell axis associates with liver fat and insulin resistance: a validation study in women with non-steatotic liver fat levels. Diabetologia 64(3):512-520.
Sujana C, Seissler J, Jordan J, Rathmann W, Koenig W, Roden M, Mansmann U, Herder C, Peters A, Thorand B, Then C. (2020). Associations of cardiac stress biomarkers with incident type 2 diabetes and changes in glucose metabolism: KORA F4/FF4 study. Cardiovasc Diabetol. 19:178
Zaharia OP, Strassburger K, Strom A, Bönhof GJ, Karusheva Y, Antoniou S, Bódis K, Markgraf DF, Burkart V, Müssig K, Hwang JH, Asplund O, Groop L, Ahlqvist E, Seissler J, Nawroth P, Kopf S, Schmid SM, Stumvoll M, Pfeiffer AFH, Kabisch S, Tselmin S, Häring HU, Ziegler D, Kuss O, Szendroedi J, Roden M; German Diabetes Study Group. (2019). Risk of diabetes-associated diseases in subgroups of patients with recent-onset diabetes: a 5-year follow-up study. Lancet Diabetes Endocrinol 7(9):684-694.
Then C, Then H, Meisinger C, Heier M, Peters A, Koenig W, Rathmann W, Scherberich J, Seissler J. (2019). Serum uromodulin is associated with but does not predict type 2 diabetes in elderly KORA F4/FF4 study participants. J Clin Endocrinol Metab jc.2018-02557.
Schloot NC, Pham MN, Hawa MI, Pozzilli P, Scherbaum WA, Schott M, Kolb H, Hunter S, Schernthaner G, Thivolet C, Seissler J#, Leslie RD#. (2016). Inverse relationship between organ-specific autoantibodies and systemic immune mediators in type 1 diabetes and type 2 diabetes: Action LADA 11. Diabetes Care 39:1932-1939.
Rottenkolber M*, Ferrari U*, Holland L, Aertsen S, Kammer NN, Hetterich H, Fugmann M, Banning F, Weise M, Sacco V, Kohn D, Freibothe I, Hutter S, Hasbargen U, Lehmann R, Grallert H, Parhofer KG, Seissler J#, Lechner A#. (2015). The diabetes risk phenotype of young women with recent gestational diabetes. J Clin Endocrinol Metab 100:E910-918.
Prof. Dr. med. Jochen Seißler Leiter der Diabeteologie Jochen.Seissler@med.uni-muenchen.de
PD Dr. med. Cornelia Then Cornelia.Then@med.uni-muenchen.de
Dr.med.vet. Lelia Wolf van Bürck Lelia.van_Buerck@med.uni-muenchen.de
Dr. Mohsen Honarpisheh Mohsen.Honarpisheh@med.uni-muenchen.de
Monika Pehl Monika. Pehl@med.uni-muenchen.de
Yichen Zhang Yichen.Zhang@med.uni-muenchen.de