The shortage of organs for transplantation
Organ transplantation is in many cases the only effective therapy for end-stage organ failure. Currently, almost 120.000 solid organ transplants are performed each year, with kidney leading the transplant race representing for almost 66% of the total procedures performed globally. However, despite the success of transplantation, it is estimated that only 10% of the global organ needs are covered. Thus, organ shortage constitutes a major global concern.
Traditionally, only organs obtained in optimal conditions have been considered for transplantation. However, the lack of organs is leading to the increased use of suboptimal grafts (e.g. non-heart beating donors), which poses new challenges. The most important hurdle preventing the clinical use of suboptimal organs is the limitation of static cold storage (SCS) ―the current gold standard for organ preservation that consists in slowing down the organ metabolism by storing it in ice. SCS is well suited for optimal grafts, but not for suboptimal ones since (i) it allows short preservation times (2-20 h), (ii) it does not provide information about the organ viability and (iii) it additionally damages the organ due to ischemia-reperfusion phenomena. Therefore, improving preservation methods becomes crucial for increasing the number of donor organs available for transplantation, the major unsolved need in this clinical field.
Methods for organ preservation
- STATIC COLD STORAGE (SCS). It is the gold standard organ preservation system. After harvesting, the organ is washed and immersed in melting ice at 4°C inside a sterile bag filled with preservation solution. By this procedure, it is possible to slow the cellular metabolism until reducing the oxygen needs of the tissues down to, approximately, 10% of physiological levels. Its main advantage is its simplicity, since it does not require technologically advanced equipment, and thus it is a cheap option. However, as has been discussed previously, this preservation method gives good results with optimal organs, which are scarce, does not provide any objective information on the viability of the organ, has short preservation periods and induces ischemia-reperfusion damage in the organ.
- HYPOTHERMIC MACHINE PERFUSION (HMP). Based also on the slowing down the organ metabolism by cooling down to 4°C, but in this case the organ is perfused by pumping the cold preservation solution, that provides oxygen and nutrients over a prolonged period. Thanks to this, it enables organ storage for a longer time and provides some improvement of the organ function after transplantation. Unlike static storage, hypothermic perfusion requires the use of specialized equipment which includes pumps, valves and a perfusion circuit to which the organ is connected. This complicates the use of the technology and significantly raises its costs. Furthermore, the clinical advantages of this method compared to SCS are not clear.
- NORMOTHERMIC PRESERVATION (NP). is based on the perfusion of the organ at 37°C with a blood-like solution that carries oxygen, nutrients and other molecules, mimicking the physiological conditions. As it explained in detail in the next section, this preservation method has the potential to solve the main limitations in the field of transplantation that are associated with SCS and HMP. The solution developed by EBERS is based on NP.
The solution proposed by EBERS in the NORMOPERF project to the current limitations of organ preservation consists in a portable medical device for organ preservation based on normothermic perfusion. Our new device is capable of maintaining human organs in a viable state for sustained periods under physiological conditions ex vivo. Such device provides 37°C temperature conditions and supplies the organ with oxygen and nutrients to mimic the in vivo conditions and maintain cellular metabolism. Furthermore, our device includes a real-time organ function monitoring system for the continuous assessment of the metabolic and secretory activity of the organ and a predictive algorithm to assess the organ viability before transplantation to the recipient. Thanks to the unique features of our medical device, it will enable extended preservation times (≥24-48 h), minimized organ injuries during preservation and the determination of organ viability. This will by itself contribute to significantly improve organ preservation, although the most important benefit that we offer is the possibility of using suboptimal organs that are currently discarded. This will be possible thanks to our organ viability prediction module, which gives the possibility of assessing the actual organ status for transplantation in an easy way, and to the use of enhanced preservation conditions, which have proved in our pre-clinical studies to partially revert pre-existing damages of preserved organs.