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SFB 738:  Optimisation of Conventional and Innovative Transplants

Subject Area Medicine
Term from 2007 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 24899777
 
Final Report Year 2020

Final Report Abstract

The focus of CRC 738 "Optimization of conventional and innovative transplants" was the development of improved (therapeutic) interventions for solid organ and stem cell transplantation. With the ongoing short-age of organs in Germany, one of the goals of transplantation medicine is to bring every available donor organ into the patient with optimal efficiency and best prognoses. After organ transplantation patients have to be treated for a lifetime with medication that drastically suppresses their immune system. This intervention is inevitably and without alternative because this is the only way an allogeneic organ can survive in the recipient without being rejected by its immune system. However, this treatment leads to drastic side effects, such as higher infection rates, higher probability of carcinogenesis, kidney dysfunction or development of diabetes. One of the outstanding findings of this research network was to identify the influence of the immunological elements of the recipient immune system in relation to the protection of transplanted organ. With the help of these regulatory immune cells, the researchers at CRC738 were able to demonstrate in preclinical models that the transplanted organs (e.g. skin, lungs, pulmonary arteries) were tolerated by the recipient immune system. The molecular understanding of the function and improvement of these cells, which has been researched by various projects of the CRC738, has also contributed to the fact that this option of therapy will be used and implemented in patients in a first worldwide clinical trial in 2020. The medical standard for the treatment of hematopoietic diseases (e.g. leukemia) is stem cell transplantation of a tissue-compatible donor. For the treatment the patient's immune system has to be completely eradicated beforehand. But even with tissue compatibility, life-threatening secondary diseases after transplantation can occur, which lead to the development of a “graft-versus-host” disease (GvHD) often resulting in systemic organ failure and finally in death. Furthermore, a stem cell transplantation completed is no guarantee for the successful treatment of leukemia. The likelihood of recurrent leukemia is too great. The scientists of CRC738 were able to develop therapies that could not only significantly reduce the probability of GvHD, but also generated strategies to prevent relapse. These forms of therapy developed in CRC738 are already part of everyday medical practice at Hannover Medical School (MHH). The third pillar of the CRC738 focused on the optimization of the grafts by its optimal preservation in the period between removal and transplantation. Techniques and methods have been developed that influence the short or long-term outcome of graft survival. With the identification of the responsible cells and the mechanisms that lead to organ damage after the so-called ischemia reperfusion injury, protocols and methods were developed that prevented this transplant damage and thus minimized damage to the organ and the associated malfunction or rejection after transplantation. In retrospect, the CRC738 has achieved remarkable and trend-setting success during its twelve-year tenure. Results from the individual CRC738 projects led to the fact that many of the findings summarized here already belong to the standard repertoire in the clinical treatment of patients at Hannover Medical School.

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