Ex-Vivo Organ Perfusion

Based on the increasing discrepancy between organ recipients and organ donors, more and more patients on the waiting list for organ transplantation die. In addition, the so-called ischemia-reperfusion injury during organ transplantation leads to acute and chronic rejection of the transplanted organs. Addressing these problems, ex-vivo organ perfusion systems (e.g. heart, lung, liver, kidney) have been developed in recent years, which on the one hand allow for greater geographic flexibility in the context of donor management, as well as allow for the re-evaluation of potential donor organs, thereby increasing the number of available donor organs. On the other hand, the organs in the ex-vivo systems can be perfused with a (body) warm nutrient solution, thus contributing to the reduction of ischemia-reperfusion injury. Consequently, this leads to improved outcomes after organ transplantation. In addition to the optimization and spectrum expansion of ex-vivo organ perfusion (e.g. limb perfusion) in the context of allogeneic (exogenous) transplantation, the advancement of modern medicine has opened up a multitude of other possible interdisciplinary ex-vivo therapeutic approaches, which the research group is working on developing and establishing. These are highly innovative strategies in the sense of regenerative, immunological, cell-based, pharmacological, as well as anti-tumor and anti-infective therapy approaches for the different, ex-vivo perfusable organs and extremities in the context of autologous (body-own) replantations.

Following the translational idea, the corresponding organ could be treated ex-vivo while the patient is connected to the corresponding organ replacement procedure (e.g. dialysis, extracorporeal membrane oxygenation) for this period for general stabilization. This is followed by autologous replantation of the organ previously treated ex vivo. In addition, the aforementioned ex-vivo therapy strategies are also established for use in the context of allogeneic, as well as xenongenic transplantations.
The working group is focused on the development, analysis and establishment of the following innovative therapeutic strategies, both in the field of allogeneic and xenogeneic transplantation, as well as autologous replantation:

a. Regenerative ex-vivo medicine / tissue engineering / cell-based therapeutic strategies.
b. Ex-vivo tumor therapy (e.g., ex-vivo radiotherapy and high-dose chemotherapy).
c. Ex-vivo immunotherapy (e.g. ex-vivo MHC silencing).
d. Ex vivo infection therapy (e.g., application of high-dose antibiotic therapy).
e. Ex-vivo gene therapy (e.g., ex-vivo correction of genetic diseases).

The wide-ranging expertise of the working group enables the respective individual and project-specific adaptation of the ex-vivo perfusion devices, such as the assessment of the ex-vivo perfused organs (e.g. heart, lungs) in CT and MRI. Likewise, the ex-vivo application enables organ- and project-specific adaptation of the ex-vivo milieu; among other things, the perfusion pressure, perfusion speed, perfusion solution and temperature can be varied accordingly.

Within the framework of interdisciplinary projects, the above ex vivo therapeutic approaches are compared and analyzed with those of in vivo therapy - this is done in both large animal and small animal models.
The advantages of ex vivo compared to in vivo therapy include the local, organ-specific limited therapy option, the absence of dose-limiting systemic side effects with the possibility of dose increase and consecutive more effective therapy, and the project-specific adaptation of the ex vivo milieu (e.g., reduction of pO2 content).