With funding from Wyss Zurich, an interdisciplinary group of researchers from ETH Zurich and the University Hospital Zurich has developed a device that significantly extends the life of donor livers outside the human body by simulating a range of bodily functions. A dSPACE MicroLabBox performs the central control tasks.
The demand for donor livers has been growing drastically for years, quickly outstripping the number of organs available. Every successful liver transplant effectively prolongs the life of a patient. This is why it is important to use all available donor livers optimally. The healthier the liver or partial liver, the better the chances are that the patient will be able to return to a normal life. This is even more likely if it is possible to preserve the donor liver longer outside of the body. And that is exactly what the new perfusion machine does.
A Race Against Time
With the perfusion machines currently available on the market, donor livers can be preserved for transplantation for a maximum of 24 hours. In order to extend this time, ideally to up to a week, an interdisciplinary team of researchers consisting of surgeons, engineers, and biologists started developing an innovative perfusion machine in mid-2015 as part of the Liver4Life project. It simulates numerous bodily functions and provides a donor liver with an environment that is as similar as possible to the conditions present in a human body. As a result, livers can not only survive up to one week outside of the body, their condition can also be improved considerably, which opens up a variety of new perspectives for future transplants. For example:
- Reliably estimating the quality of the donor livers based on measurement data
- Improving the quality of previously damaged livers
- Potentially regenerating parts of a liver in the future
- Making autologous organ donations possible
Ultimately, the available donor livers can be used much more efficiently as a result, or they are not even required in the first place (in the case of an autologous donation).
Artificial circulation for organs
Nature as a Role Model
In order to preserve a liver outside the body, it used to be common practice to pack it in ice, known as static cold storage, to reduce the metabolic processes to a minimum. However, to achieve the goals described above, it is necessary for all biochemical processes in the donor liver to continue as if it were still in the body. For this purpose, the metabolic functions of the liver had to be described in detail from a medical perspective so that engineers could then implement the requirements in a machine. Five key functions in particular were identified for long-term perfusion: controlling the glucose metabolism, preventing hemolysis (the rupture of red blood cells), discharging waste, controlling the supply of oxygen through the perfusate (fluid used for the artificial perfusion of organs, blood in this case), and simulating diaphragm movements.
New Habitat for a Liver
In the human body, the liver is fed through two blood vessels, in which both the blood pressure and the share of oxygen, hormones, and nutrients in the blood vary. Outside of the body, the Liver4Life perfusion machine takes care of all this. If the donor liver is connected to the machine, it is not simply fed a standard supply of nutrients, neurotransmitters, and oxygen. Instead, this supply is adjusted to the liver’s needs. Waste produced by the liver metabolism is discharged by means of dialysis or as bile. The fluid leaving the liver is fed back into the system. To make sure the liver feels “at home”, a series of sensors transmit the data that is used as a basis to adjust the supply to the liver via various actuators. In addition, sensors monitor its condition at all times. What is more, an artificial diaphragm simulates the movements of a real diaphragm to protect the liver from pressure necrosis (tissue dying as a result of constant pressure). Such a setup requires various subcircuits, which all have to be carefully calibrated.
The MicroLabBox controls how the sensors and actuators interact with each other. In doing so, it takes over the function of the brain by coordinating the simulation of the different organs.
Multiple Functions, One Control Unit
A MicroLabBox serves as the control unit used to simulate the brain functions required in this context. One of these boxes is being used at ETH Zurich in the field of automotive developments, which means they already had experience using it. The MicroLabBox stood out due to its flexibility and high computing power. The MicroLabBox acts not only as an I/O interface for the communication between sensors and actuators, but also as the central computation unit. The work is supported by the dSPACE experiment software ControlDesk, which makes it possible to access real-time applications while they are running. As a result, it is possible not only to monitor the supply parameters of the liver but also to influence them actively when a donor organ is connected to the machine.
Better Simulation for Better Quality
The perfusion machine considerably expands the possibilities of maintaining the metabolic functions of a donor liver outside of the human body. What are the next steps after these promising results? Clinical studies are now required to demonstrate that even mediocre livers can actually be transplanted after undergoing the perfusion process. The metabolic data delivered by the perfusion machine could provide a reliable evaluation of the organ quality. In the long term, the liver’s enormous capacity to regenerate itself will also be used so that one donor liver can benefit multiple patients at once. It would also be conceivable – for example, with cancer patients – to remove healthy parts of the liver, regenerate them in the Liver4Life machine, and retransplant them as a replacement for the diseased organ. This would not only potentially save the patient’s life, it would also save them from having to take medication for the rest of their life to prevent their body from rejecting a new organ. A donor liver would not be required in this case. Thanks to the new perfusion machine, there is a renewed hope that more lives can be saved by making better use of quality donor livers or even with autologous organ donations.
Courtesy of ETH Zurich, the University Hospital Zurich, and the Wyss Zurich Institute
When it’s a matter of survival, there are no ‘pretty good’ results. The decision as to whether or not a donor organ can be transplanted, for example, has to be definitive and reliable. The perfusion machine, supported by the MicroLabBox, makes it possible to make decisions like this.
About the authors:
Dr. med. Dilmurodjon Eshmuminov
University Hospital Zurich, Zurich, Switzerland, Department of Visceral and Transplantation Surgery, contributes his medical expertise to the project team and is responsible for defining the medical requirements
Dr. Dustin Becker
ETH Zurich, Wyss Zurich, Zurich, Switzerland, helped develop the system as part of his dissertation and is responsible for implementing the medical requirements in the machine.