Everyone should participate in innovations – invisible organs have what it takes to do so: by an organ care center as interface between donor and recipient.

Network Targets

Despite all the progress made in modern transplantation medicine, organ rejection, the severe side effect of lifelong immunosuppression and a shortage of donor organs remain the major problems in transplantation. Transplantation research to improve transplant outcome continues to focus on modifying the recipient's immune system to achieve an immunological blindness to the transplant. However, this immunological blindness is not donor-specific but is achieved through a general suppression of the competence of the recipient immune system. General immunosuppression represents the greatest burden for transplanted patients as it is associated with severe side effects such as tumor development, life-threatening infections and nephrotoxicity.

The immunogenicity of a transplant is determined by the gene products of the Major Histocompatibility Complex (MHC), which in humans are referred to as Human Leukocyte Antigens (HLA). The mechanism by which the immune system recognizes allogeneic cells as foreign is based on the recognition of these HLA-antigens on the cell surface by cytotoxic T-cells and antibodies. The HLA antigens are extremely polymorphic, so that thousands of variants exist which trigger organ rejection in case of a mismatched organ transplant. But even in the case of an extremely rare complete HLA match between donor and recipient, rejection occurs regularly because short peptides from all endogenous proteins are presented in the HLA molecules, which exhibit countless disparities between genetically distinct individuals and are referred to as minor histocompatibility antigens (mHag). 

The common goal of the innovation network is a completely new approach to solving the problem of rejection: instead of inducing immunological blindness in the organ recipient through immunosuppression, this project aims to create immunological invisibility of the donor organ. This goal is to be achieved by reducing the immunogenicity of donor organs by genetically targeting and permanently switching off the tissue markers during the ex vivo phase of the organ to be transplanted. As a result, the target structures for immunologically mediated rejection are missing, so that an organ can no longer be recognized as foreign. The results of the innovation network should provide the basis for a subsequent clinical study and enable the application in humans. To this end, an Organ Care Center is being planned as an interface between organ allocation and transplantation. 

Future Vision

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With an Organ Care Center as an interface between organ allocation and transplantation, the transplants could be modified ex vivo prior to their further distribution to the recipient centers in such a way that they are immunologically invisible and therefore not rejected.

Gender and Diversity Equality

Gender- and Diversity-Sensitive Medicine

To date, women have been disadvantaged in transplant medical care because they are more frequently exposed to immunization events than men due to previous pregnancies. The resulting higher incidence of antibodies against tissue markers leads to longer waiting times on transplant lists, higher rejection rates or more intensive immunosuppression in women. By modifying the organs to be transplanted, the influence of the immunization level of the recipients is minimized, neutralizing the disadvantage of women in organ allocation and achieving gender equality. 

In addition to this gender concern, a further inequality of opportunity exists in transplant medical care for people with a migration background. This is related to the ethnic diversity of the tissue markers, which leads to a higher incidence of organ-rejecting antibody formation due to a higher inequality rate in the tissue markers between patient and recipient. By modifying the organs to be transplanted, the influence of donor/recipient dissimilarity is minimized, resulting in equal opportunities for all patients regardless of ethnic origin.