Organ Recovery

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Background
Liver transplantation is the treatment of choice for patients with advanced liver cirrhosis, hepatocellular carcinoma within the Milan-criteria, and severe metabolic or autoimmune hepatic disorders. However, the number of patients waiting for liver transplantation by far exceeds the number of available donors. Especially in Germany, the success of liver transplantation is limited by a dramatic decline in organ donations since 2010, which led to a more restrictive listing, increasing number of patients with high MELD on the waiting list, and thus negatively affecting the outcome of liver transplantation. Strategies to increase the number of available liver grafts are based on living-related liver donation and on the usage of marginal grafts from so-called extended criteria donors (ECDs), which are defined as grafts that carry a high risk of impaired function, technical complications, or the transmission of infection or malignancy to the recipient [4,5]. Donation after Cardiac Death (DCD), which is performed in other European countries and North America in order to increase the donor pool, is prohibited by law in Germany.
Normothermic Extracorporeal Liver Machine Perfusion

Liver machine perfusion was initially considered in the earlier years of transplantation for organ preservation but rediscovered within the last years as concept to improve the quality of marginal grafts. Clinically applicable machine perfusion concepts for the liver mainly differ in regard to their perfusion temperature:

In hypothermic (HMP) or subnormothermic machine perfusion (SNMP), the liver graft is perfused at temperatures ranging from 1 – 21 °C. Under these conditions, the increased solubility of oxygen facilitates the use of perfusate solutions without oxygen carriers. HMP of liver grafts is currently under clinical evaluation: Guarrera et al. showed less early graft dysfunction and lower enzyme release after end-ischemic hypothermic machine perfusion of livers from brain-dead donors (DBD) compared to static cold preservation. Dutkowski et al. performed hypothermic oxygenated machine perfusion (HOPE) of DCD liver grafts and showed that it was effective against reperfusion injury. Hoyer et al. recently reported a clinical series of machine-assisted slow controlled oxygenated rewarming of cold-stored DBD livers, resulting in 50% reduction of the peak serum transaminases after transplantation compared to untreated controls.

Normothermic machine perfusion (NMP) at 37°C, in contrast to perfusion at lower temperatures, necessitates the use of oxygen carriers, mainly red blood cells . NMP maintains the graft in a near-to-physiological state, which avoids the depletion of cellular energy and accumulation of waste products, and thus minimizes the preservation injury. Ravikumar et al. and Selzner et al. recently demonstrated the safety and feasibility of NMP in phase 1 clinical trials in Europe and North America. A phase 3 randomized controlled clinical trial is currently being performed to compared NMP to static cold storage.

PD Dr. Raschzok and his team have established a lab-scaled, portovenous murine liver perfusion system similar to the setup described by Tolboom et al. The perfusion system consists of a pressure-controlled roller pump, an oxygenator and a custom-made perfusion chamber. As perfusate, Dulbecco's Modified Eagle´s Medium (DMEM) substituted with rat erythrocytes, rat plasma and HEPEs buffer was used. Heparin was continuously infused into the perfusate.

  • Schematic of the machine perfusion system
  • Perfusion system during an experiment
  • Setting up an experiment

The addition of erythrocytes led to significantly lower transaminase secretion but to potassium excess >14 mmol/L in the perfusate. The inclusion of a miniaturized oxygenator, a dialysis circuit, the decrease of the perfusate from 100 to 50ml, and the increase of the hematocrit from 7 to 15% resulted in significantly lower transaminase secretion , normal potassium levels and a preserved liver architecture in Hematoxylin & Eosin (H&E) staining after 6 hours of perfusion.
Evaluation of the liver perfusion system is currently still ongoing. PD Dr. Raschzok plans on proving the efficacy of the system through validation in future transplantations experiments of perfused rat livers.

  • Rat Liver | H&E | 100x | First trials with high rates of necrosis
  • Rat Liver | H&E | 100x | Improved perfusion system

Our Team

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Nathanael Raschzok

Surgeon scientist and principal investigator of the Organ Recovery Group

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Joseph Gassner

Research Assistant

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Simon Moosburner

Medicine Student

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Maximilian Nösser

Medicine Student

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David Wyrwal

Medicine Student

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Felix Claussen

Medicine Student

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Julian Pohl

Medicine Student

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