Enter machine perfusion in organ transplantation: an advanced technique that holds the promise of revolutionizing organ transplantation by addressing the limitations of traditional preservation methods and offering additional benefits in organ repair and immunomodulation.
In this article, we delve deep into the world of machine perfusion in organ transplantation, exploring its role in various organ transplantations, ex vivo monitoring, viability assessment, immunomodulation, and repair. We also examine the current clinical use of machine perfusion in organ transplantation and its future developments, including its adoption starting in the Netherlands and the methodological challenges that need to be overcome to fully harness its potential.
Short Summary
- Machine perfusion is a technique employed in organ transplantation that offers enhanced preservation, real-time monitoring, and potential for organ repair.
- It provides advantages over static cold storage such as continuous solution supply and longer preservation time.
- Machine perfusion has revolutionized the field of organ transplantation by improving graft quality and patient outcomes with its use in kidney, liver, lung & heart transplants.
The Role of Machine Perfusion in Organ Transplantation
As the demand for organ transplantation grows, so does the need for innovative techniques that maximize the quality and viability of donor organs. Machine perfusion, is one such technique, offering enhanced preservation, real-time monitoring, and potential for organ repair and immunomodulation, particularly in solid organ transplantation. This advanced method addresses the limitations of static cold storage, such as the buildup of toxic waste products, restoration the energy deficit in the graft and minimization of ischemia-reperfusion injury which can be seen after transplant.
In the following subsections, we will explore how machine perfusion overcomes the limitations of static cold storage and discuss the different types of machine perfusion techniques employed in organ transplantation.
Overcoming Limitations of Static Cold Storage
Machine perfusion offers several advantages over static cold storage, including:
- Continuous supply of preservative solution, decreasing the risk of ischemia/reperfusion injury
- Longer preservation time
- More effective means of cooling the donor organ
- Elimination of metabolic and toxic waste products
- Reduced risk of graft failure after transplantation
Types of Machine Perfusion
There are two main methods of machine perfusion: hypothermic and normothermic perfusion. Hypothermic Machine Perfusion (HMP) involves the use of temperatures lower than the physiological range, while Normothermic Machine Perfusion (NMP) employs temperatures within the physiological range. The choice of method depends on the type of organ being preserved and its specific preservation requirements.
HMP is especially beneficial for cooling the donor organ and reducing the risk of graft failure after transplantation. In contrast, NMP maintains the organ in a physiologically and metabolically active state, thus enabling potential organ repair and reconditioning. This is particularly advantageous for donor organs that require reconditioning, such as extended criteria donor organs.
Key Applications of Machine Perfusion
Machine perfusion has shown promising results in various organ transplantations, such as:
- Kidney transplants
- Liver transplants
- Lung transplants
- Heart transplants
By improving graft quality and patient outcomes, this technique is paving the way for a new era in organ transplantation.
In the upcoming subsections, we will discuss the application of machine perfusion in:
- Kidney transplantation
- Liver transplantation
- Lung transplantation
- Heart transplantation
This innovative technique has made a significant impact on the field.
Kidney Transplantation
Kidney transplantation is one area where machine perfusion, particularly hypothermic machine perfusion, has demonstrated significant benefits. The Machine Perfusion Trial of the Consortium for Organ Preservation in Europe (COPE) revealed that non-oxygenated HMP provides superior graft survival benefits when compared to static cold storage (SCS). In addition, it was demonstrated to decrease delayed graft function (DGF) in all deceased donor kidneys. Hypothermic oxygenated perfusion is another technique being explored for organ preservation.
Machine perfusion is now widely accepted as the preferred method for preserving kidneys, even for those at higher risk. Examples include kidneys from expanded criteria donors, donors older than 65 years, and donors after circulatory death. Studies have shown that kidney transplants after hypothermic machine perfusion had lower rates of delayed graft function and shorter hospitalization compared to kidney transplants retrieved with the SRR technique.
Liver Transplantation
Liver transplantation is another area where machine perfusion. Research has indicated that machine perfusion technology can enhance the quality of donor organs, lessen ischemia-reperfusion injury, and reduce the likelihood of primary non-function.
Hypothermic and Normothermic machine perfusion has been shown to be safe and feasible in liver transplantation, with the potential to:
- Reduce biliary complications
- Improve survival rates
- Lower discard rates
- Lessen early allograft dysfunction
Machine perfusion can greatly impact the success of liver transplantation.
Lung Transplantation
Lung transplantation is yet another field where machine perfusion has made a significant impact. Ex vivo prolonged lung preservation has demonstrated successful transplantation of high-risk donor lungs, and machine perfusion has become an essential tool for assessing lung graft quality from an uncontrolled donation after circulatory death.
Ex vivo lung perfusion (EVLP) is a technique used for pulmonary grafts that did not meet standard lung criteria initially. Clinical experience with machine perfusion of the lung has shown that maintaining the organ in a physiologically and metabolically active state is crucial. The number of transplantable lungs obtained through ex vivo perfusion, specifically ex-vivo lung perfusion (EVLP), is approximately 80% across all reported series. This overall yield is quite significant.
Heart Transplantation
While machine perfusion has been utilized in heart transplantation, its clinical application is still restricted to a few centers. The Transmedia Organ Care System (OCS). The heart is a medical device utilized for the machine perfusion of donor hearts, maintaining them in a warm, beating, near-physiological state prior to transplantation.
Several clinical trials, including the PROCEED trial and the International Expand Heart Pivotal Trial, are currently exploring the potential of OCS in human heart transplantation. These trials aim to evaluate the quality of heart transplantation from donors that do not meet current standard acceptance criteria.
Ex Vivo Monitoring and Viability Assessment
Machine perfusion enables real-time monitoring of organ function and quality, providing valuable information on the viability and transplantation potential of donor organs. Despite the availability of numerous biomarkers and functional parameters, determining highly predictive cut-offs for organ acceptance or rejection during machine perfusion remains challenging.
In the following subsections, we will delve into the various biomarkers and functional parameters that can be monitored during machine perfusion, as well as the challenges in establishing predictive cut-offs for organ acceptance or rejection.
Biomarkers and Functional Parameters
Various biomarkers and functional parameters can be monitored during machine perfusion, providing objective indications of organ quality and function. Flow and intrarenal resistance are important parameters that can be used to predict post-transplant outcomes. Perfusion plays an important role in determining the success of such predictions.
Hosgood et al developed a quality assessment score targeting NMP. This score is based on indicators such as macroscopic perfusion, renal blood flow, and urine output. By monitoring these parameters, transplant teams can make informed decisions on the suitability of donor organs for transplantation.
Challenges in Establishing Predictive Cut-offs
Determining highly predictive cut-offs for organ acceptance or rejection during machine perfusion remains a significant challenge. Establishing the most suitable cut-off value for a diagnostic test with continuous results, as well as considering the effects of varying cut-off times on the performance metrics of the model, such as sensitivity, specificity, and predictive values, is crucial.
Furthermore, ensuring appropriate analytic decisions and acquiring sufficient and relevant data for predictive modeling are essential challenges that must be addressed. By overcoming these challenges, the potential of machine perfusion in enabling precise and informed organ transplantation decisions can be fully realized.
Challenges and limitations of machine perfusion
While machine perfusion has several benefits over traditional cold storage, there are still some challenges and limitations associated with the technique. One of the main challenges is the cost and availability of the technology. Machine perfusion devices can be expensive, and not all transplant centers have access to the technology.
Another challenge is the complexity of the technique. Machine perfusion requires specialized training and expertise, and not all transplant teams may have the necessary skills and resources to perform the technique.
That’s where UC Health’s Transplant program – with 55 years of experience – makes all the difference. UC Health provides Greater Cincinnati’s only comprehensive adult organ transplant center, located at UC Medical Center making them the most well equipped to utilize machine perfusion as a way to promote better patient outcomes for transplant patients. The program is nationally known for transplant clinical practice, research, and education. It is also a destination referral center, with more than 1,800 referrals received in 2022 for kidney and liver transplant patients. With more than five decades of research and training, 25+ providers, and 10 clinics within 120 miles of Cincinnati, UC Health provides the care you deserve close to home.
Immunomodulation and Repair During Machine Perfusion
Machine perfusion offers several benefits in organ transplantation, including:
- Preserving donor organs
- Providing a platform for targeted immunomodulation and organ repair
- Delivering molecular and cellular treatments directly to organs during perfusion
- Improving transplant outcomes
- Revolutionizing the field of organ transplantation
In this section, we will explore the potential of stem cell therapies and anti-inflammatory agents and gene delivery techniques in immunomodulation and organ repair during machine perfusion.
Stem Cell Therapies
Mesenchymal stem cells (MSCs) show promise in improving transplant outcomes through:
- Facilitating repair of pre-preservation donor-related injury
- Downregulating local intragraft inflammation
- Reducing graft immunogenicity
- Making the grafts less vulnerable to ischemia-reperfusion injury and rejection in the recipient.
However, the exact mechanisms by which MSCs exert their beneficial effects remain unclear, and further research is needed to optimize their use in organ transplantation. By understanding these mechanisms, stem cell therapies could play a crucial role in enhancing the success of organ transplantation.
Anti-inflammatory Agents and Gene Delivery
Machine perfusion enables the delivery of anti-inflammatory agents and gene therapies directly to the organ, allowing for more precise and efficient distribution of these treatments. By reducing immunogenicity and improving long-term outcomes after transplantation, these therapies can significantly impact the success of organ transplantation.
Some strategies investigated for immunomodulation during machine perfusion include:
- the application of stem or progenitor cells
- the administration of anti-inflammatory/immunomodulatory drugs and agents
- gene transduction by adenoviral vector gene delivery
As our understanding of these therapies grows, so too will their potential in revolutionizing organ transplantation.
Current Clinical Use and Future Developments
Machine perfusion is increasingly being adopted in clinical practice, with the Netherlands implementing hypothermic machine perfusion as the standard of care for deceased donor kidneys. As more centers adopt this innovative technique, the potential of machine perfusion in organ transplantation will continue to grow.
In this section, we will discuss:
- The current clinical use of machine perfusion
- Its adoption in the Netherlands
- The technological advancements and methodological challenges must be addressed to fully realize the potential of machine perfusion in organ transplantation.
Machine Perfusion Adoption in the Netherlands
In the Netherlands, normothermic regional perfusion (NRP) and hypothermic machine perfusion (HMP) have been established as the standard of care for deceased donor kidneys. Implementing machine perfusion has led to a significant improvement in kidney transplantation outcomes in the country.
Several studies have been conducted on liver and kidney transplantation, such as the following:
These studies further highlight the potential of machine perfusion in organ transplantation. As more countries adopt machine perfusion as a standard of care, its potential in revolutionizing organ transplantation will become even more apparent.
Technological Advancements and Methodological Challenges
Technological advancements in machine perfusion, such as normothermic perfusion technology and organ-directed reconditioning, have enabled the preservation of donor organs in a more physiologically compatible state, improving transplantation outcomes. However, several methodological challenges remain, including maintaining acid-base equilibrium, providing optimal nutrition for organ weight-induced pressure, addressing electrolyte shifts, and preventing hemolysis during perfusion.
By addressing these challenges and further refining machine perfusion techniques, the full potential of this innovative technology in organ transplantation can be realized, ultimately leading to improved patient outcomes and a greater number of successful transplantations.
Future prospects
As machine perfusion continues to evolve and improve, it holds great promise for increasing the availability of high-quality organs for transplant recipients. One of the most significant developments in machine perfusion is the use of artificial intelligence (AI) to predict the viability of organs. AI algorithms can analyze data from machine perfusion devices to predict whether an organ will be viable for transplantation. This could potentially reduce the number of discarded organs and further improve outcomes for transplant recipients.
Final Thoughts
Machine perfusion represents a significant advancement in the field of organ transplantation, offering enhanced preservation, real-time monitoring, and potential for organ repair and immunomodulation. By addressing the limitations of traditional preservation methods and providing a platform for targeted therapies, machine perfusion can revolutionize organ transplantation and improve outcomes for the countless patients waiting for a life-saving transplant.
As more centers adopt machine perfusion and researchers continue to refine their techniques and explore their full potential, the future of organ transplantation looks brighter than ever, paving the way for increased organ availability and improved long-term outcomes for transplant recipients.
Frequently Asked Questions
What is the function of a perfusion machine?
A perfusion machine performs the essential function of keeping donated organs warm and alive by continuously pumping blood through them, which is known as normothermic perfusion.
This process is critical for successful organ transplantation, as it helps to preserve the organ’s viability and function until it can be transplanted into a recipient.
What is a perfusion pump for organs?
A perfusion pump is a machine used to maintain the viability of an organ outside the body by continuously pumping blood or an artificial blood substitute through it. This process is known as normothermic perfusion and can keep organs viable for weeks.
What is perfusion fluid for transplantation?
Perfusion fluid is a specialized medium that can be used for preserving kidneys prior to transplantation, which is provided in the form of Custodial HTK Solution - Cardioplegia.
This solution is designed to provide optimal protection for the organ during the transplantation process and is used to reduce the risk of organ rejection. It is also used to reduce the risk of infection and other complications associated with the transplantation process.
How does machine perfusion differ from static cold storage?
Machine perfusion offers more benefits than static cold storage, as it provides a continuous supply of preservative solution to prevent ischemia/reperfusion injury and enables extended preservation time.
It helps to maintain the quality of the organ, allowing for better outcomes for transplant patients. It also reduces the risk of infection and improves the success rate of transplantation. Additionally, machine perfusion can reduce the cost of organ preservation and storage.
What are the main applications of machine perfusion in organ transplantation?
Machine perfusion is widely used in kidney, liver, lung, and heart transplantation to improve graft quality and patient outcomes.