Organ preservation refers to the techniques used to maintain the viability and function of organs outside the body after their removal from a donor and before transplantation into a recipient. The primary objective is to minimize damage to the organ during this period, ensuring it remains healthy enough to function optimally once transplanted. This process is a core element in modern transplant medicine, impacting the success of life-saving procedures. It provides a window of time for logistical coordination and recipient preparation.
The Role of Organ Preservation
Organ preservation addresses key challenges in organ transplantation. A major hurdle is the limited time an organ can remain viable outside the body, often referred to as “ischemic time” or “cold ischemic time.” This period begins when blood flow to the organ is interrupted and ends when it is reperfused in the recipient. Different organs tolerate varying periods of cold ischemia; for example, hearts can typically be preserved for 4-6 hours, livers for 12-15 hours, and kidneys for up to 24 hours.
Prolonged ischemic time can lead to cellular damage, including oxidative stress and inflammation, resulting in delayed graft function or primary graft non-function after transplantation. Organ preservation techniques slow down the organ’s metabolic processes, reducing its need for oxygen and nutrients. This extended window allows for logistical steps such as transporting organs, performing laboratory tests, and ensuring proper donor-recipient matching.
Extending preservation time increases the pool of potential donors and recipients, making more transplants possible. Without effective preservation, strict time constraints would severely limit transplantation. By mitigating the impact of ischemia, preservation methods enhance the likelihood of a successful transplant and improve long-term outcomes for patients.
Current Preservation Techniques
Established methods for organ preservation focus on reducing metabolic activity to slow cellular degradation. Static Cold Storage (SCS) is a traditional method, valued for its simplicity and cost-effectiveness. In SCS, organs are flushed with a cold preservation solution and stored on ice at hypothermic temperatures, typically between 0-5 degrees Celsius. This hypothermia lowers the organ’s metabolic rate, decreasing its oxygen demand and energy consumption.
Commonly used preservation solutions for SCS include University of Wisconsin (UW) solution and Histidine-Tryptophan-Ketoglutarate (HTK) solution. UW solution, introduced in the 1980s, is an isotonic, high-potassium solution with components like lactobionic acid, raffinose, and hydroxyethyl starch to prevent cell swelling, plus glutathione and adenosine to support metabolic recovery. HTK solution, developed as a cardioplegia solution, has lower potassium content and reduced viscosity, which allows for a more effective initial flush of the organ’s microcirculation. While SCS is widely adopted, its limitations include finite preservation time and the inability to assess organ viability or perform reconditioning before transplantation.
Machine Perfusion (MP) is an advanced and increasingly utilized technique providing dynamic preservation. This method continuously flows a preservation solution through the organ, offering several advantages over SCS. Hypothermic Machine Perfusion (HMP), a common form of MP, maintains the organ at low temperatures (4-10 degrees Celsius) while continuously supplying nutrients and removing waste. This continuous flow reduces ischemia-reperfusion injury, prolongs preservation time, and maintains cellular integrity. HMP has demonstrated benefits like lower rates of delayed graft function in kidney transplants and reduced biliary complications in liver transplants compared to SCS. While more complex and costly, HMP allows for a controlled environment and some organ assessment during preservation.
Advancements in Preservation Science
Innovations in organ preservation science aim to extend viability and improve outcomes. Normothermic Machine Perfusion (NMP) is an advancement that mimics the body’s physiological environment. Unlike hypothermic methods, NMP maintains the organ at or near body temperature (around 37 degrees Celsius) using an oxygenated blood or specialized solution. This allows the organ to remain metabolically active, enabling functional assessment and potential repair or reconditioning before transplantation. NMP has shown promise in improving the preservation and viability of marginal organs, such as those from donation after circulatory death (DCD) donors, and may reduce post-transplant complications.
Researchers are also exploring novel preservation solutions and additives to enhance organ protection. These new chemical cocktails or supplements are designed to further protect organs from damage during the preservation period. Examples include adding antioxidants, iron chelators, or specific growth factors to existing solutions, aiming to mitigate ischemia-reperfusion injury at a molecular level. Some solutions, like Hypertonic Citrate Adenine (HC-A) solution, incorporate components such as mannitol to prevent cellular edema and oxidative stress.
Beyond temperature-controlled perfusion and improved solutions, other forward-looking technologies are being investigated. Supercooling involves cooling organs to sub-zero temperatures (e.g., -4 to -6 degrees Celsius) without ice crystal formation, which is typically damaging to tissues. This technique, often achieved by infusing organs with anti-freeze compounds, has shown potential to significantly extend preservation times for organs like the liver, from typical hours to over a day. Cryopreservation, or long-term freezing at ultra-low temperatures like -196 degrees Celsius, remains largely experimental for whole organs due to the challenge of preventing ice damage, but it is an area of ongoing research for future applications.