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| Home > Zentren > Universitäres Herzzentrum Hamburg (UHZ) > Klinik und Poliklinik für Herz- und Gefäßchirurgie > Forschung > Transplant and Stem Cell Immunobiology Lab (TSI) > Ongoing basic research projects

Ongoing basic research projects

Transplant Immunology of Solid Organ Transplantation

Research in this area concentrates on weakening the immune response to allow foreign organ and tissue transplants. Our projects focus on the basic biology of immune cell nonreactivity (tolerance) to foreign organs and tissues, the role of Th17 cells in cellular and humoral rejection and specific T cell modulation as well as gene therapy for modulating the immunogenicity of transplanted organs as well as on the use of new immunomodulatory agents to promote transplant acceptance without endangering patients' abilities to resist infections.

Brief overview of our current projects:

• The regulation of TH17 cells by TH1 cells and Tregs in graft rejection.
• The influence of immunosuppressive drug classes on TH17 development.
• Inhaled immunosuppression after lung transplantation (mechanisms behind local immunosuppression).
• Characterizing new immunosuppressive classes to prevent acute and chronic allograft rejection (e.g. JAK3 inhibition, Syk inhibition, potassium channel inhibition).
• Immunosuppressive agents for stent coating.

Immunobiology of Stem Cell Transplantation

We can apply our knowledge of transplant immunology to the field of stem cell transplantation in the hope that this will provide new therapeutic options in the future.

Congestive heart failure is the leading cause of death in the United States and Western Europe. Therapeutic options for end-stage heart failure include heart transplantation as well as stem cell transplantation to regenerate the damaged myocardium.

A variety of cell types including skeletal myoblasts, neonatal cardiac myocytes and adult stem cells have been investigated for the regeneration of injured myocardium by cellular transplantation. However, there is little reproducible evidence that any of these cells differentiate into cardiac myocytes or significantly improve myocardial function. We have investigated cellular transplantation of adult mesenchymal stem cells for the treatment of congestive heart failure following myocardial infarction and have observed limited cell survival and non-relevant improvement in myocardial function. Embryonic stem cells (ESC) theoretically hold the most promise for the treatment of heart failure since they are the most pluripotent precursor cells known.

However, there is a need to better understand how immunologically mediated rejection and non-immunological factors such as ischemia and inflammation affect survival and differentiation of ESCs. Importantly, factors that may effect the survival of intramyocardially delivered cells is a fundamental issue that has not been adequately assessed. The tracking and assessment of cell survival with novel in vivo imaging modalities must be correlated with changes in myocardial function following transplantation. We aim to characterize the type and intensity of the recipient immune response to transplanted stem cells, correlate this immune response with changes in cardiac function, establish the influence of innate immunity on transplanted cell survival and determine the effects of antigen independent factors (such as ischemia, non-specific inflammation and apoptosis) that effect stem cell survival following transplantation.

Brief overview of our current projects:

• Adult mesenchymal stem cells: homing and survival
• Immunobiology of stem cells
• Gender differences is stem cell transplantation
• Gene therapy to improve stem cell survival after transplantation