Liver Transplantation and Normothermic Machine Perfusion

Project leaders: Felix Oldhafer / Oliver Beetz

Liver transplantation is regarded as the first-line treatment for different end-stage liver diseases.

Due to an ongoing organ shortage, leading to an increased transplantation of extended donor criteria organs and an often poor condition of the recipients, current clinical strategies are in need of optimization.

Our workgroups aims to evaluate normothermic machine perfusion for individualized optimization of liver grafts in a porcine model.

Hepatocyte Transplantation

Project leaders: Oliver Beetz / Felix Oldhafer

Hepatocyte transplantation (HCTx) is a promising therapy option for the treatment of numerous inborn and acquired liver diseases. HCTx is much more cost efficient and a less invasive procedure than conventional liver transplantation. Furthermore, the method of cell transplantation enables the opportunity of pre-Tx modification of hepatocytes by technologies such as gene therapy. Unfortunately, the promising results obtained in animal models could not be successfully transferred into clinical application in man, yet. The aim of our project is to evaluate the immunological aspects of HCTx in murine and porcine models in order to establish new strategies for efficient cell transplantation with optimized long-term outcome.

Isolation, Culture and Cryopreservation of Primary Human Hepatocytes

Project leaders: Felix Oldhafer / Oliver Beetz

Large quantities of primary human hepatocytes (PHH) are required for basic research and clinical applications. In addition, they represent a valuable tool used in pharmacotoxicology. In conclusion, the demands for PHH continuously increase while their supply is insufficient due to limited cell sources. The aim of our project is to evaluate alternative sources of liver tissue for the isolation of high quality primary human hepatocytes. Furthermore, we are interested in innovative concepts for long-term cell culture and cryopreservation of PHH in order to optimize the supply with liver cells for further use in vitro and in vivo.

Infrastructure: Primary Human Hepatocyte (MHH) / Humanized Mouse (UKE) Core Facility

Infrastructure coordinator: Florian Vondran

Located at Hannover Medical School (MHH), the Primary Human Hepatocyte (PHH) Core Facility provides research groups within the German Centre for Infection Research (DZIF) with hepatocytes freshly prepared from human liver tissue. The isolation of PHH is a standardized, technically complex procedure and PHH are only of limited availability. Along with PHH, cell populations from the non-parenchymal fractions and liver stem cells can be obtained upon request. However, hepatocyte functionality is rapidly lost in vitro and there is there is an urgent need to create a scientific infrastructure dedicated to the generation of in vivo systems enabling infection studies and long-term antiviral drug evaluation. Thus, the unit recently has merged with the Humanized Mouse Platform lead by Prof. M. Dandri at UKE to serve as a new competitive technological platform enabling in vitro and in vivo infection studies with human hepatotropic viruses and preclinical evaluation of new therapeutic concepts within the Thematical Translation Unit Hepatitis as well as to support other Thematical Translation Units within DZIF.

Retrospective data collection and analysis in abdominal transplantation and hepatobiliary and pancreatic surgical oncology

Project leaders: Oliver Beetz / Felix Oldhafer

The Hannover Medical School is one of Germany’s largest solid organ transplant centers and a tertiary referral center for hepatobiliary and pancreatic malignancies.

As such, our workgroup aims to further improve perioperative outcome in our patients by collecting and analyzing large data registries enabling surgical quality control and the validation of new hypotheses.

In vivo ablation of single cells in the liver before ablation and at various time points after ablation.

Longitudinal imaging and laser manipulation in vivo using an abdominal imaging window

Project leaders: Daphne DeTemple / Stefan Kalies (NIFE)

The liver is known to possess extensive regenerative capabilities, the processes and pathways of which are not fully understood. In order to gain a better understanding of liver regeneration, we combine longitudinal imaging analysis  in vivo through an abdominal imaging window in the mouse with simultaneous manipulation on a single cell level.

Schematische Darstellung einer Kombination optischer Techniken, wie der hyperspektralen Bildgebung, und künstlicher Intelligenz.

In vivo imaging of organs via endoscopic, fiber based fluorescence and hyperspectral microscopy

Project leaders: Stefan Kalies (NIFE) / Daphne DeTemple

Our approach of guided tissue imaging in vivo permits the acquisition of microscope like images. The use of a small imaging fiber endoscope to gain multi-colour images allows for minimally invasive, recurrent imaging sessions. 

Fiber-based endoscopic in vivo visualization of jejunum, fat, blood vessel in the abdominal muscle, liver, pancreas with zoom-in on detailed structure in GFP-expressing mice.

Hyperspectral imaging

Project leaders: Daphne DeTemple / Stefan Kalies (NIFE)

Hyperspectral imaging generates images of the analysed tissue via recording of the microscopic structure with simultaneous detection of the reflection spectrum of every pixel. With this approach, a label-free evaluation of the tissue composition is possible (i.e. without further staining).