Transplants are a miracle of modern medicine, but the lack of available organs creates a significant medical burden on society. The discrepancy in supply vs demand is partially due to a shortage of suitable donated organs, but it also stems from a lack of preservation capabilities. Preservation at cryogenic temperatures has the potential to solve this problem, as it has become well-established as a means of preserving living cells and tissues. Cryonics, on the other hand, refers to the cryopreservation of primarily human beings (whole-body or neuropreservation) and also animals. Cryonics research can add valuable insight into the preservation of biological materials, like tissues and cells, which aids in advancements in organ preservation. Implementing cryopreservation procedures in organ transplantation and introducing cryobanks could be revolutionary for patients and medical staff globally.
Stop the Clock
The challenge that presents itself with organ transplants today—as is the case with most cryo-related procedures—is time. Once a surgeon removes a kidney from a body, it can remain viable for about 36 hours; livers are up to 16, and hearts survive a mere three to five hours. Without time on their side, medical teams have hours at most to match an organ with a recipient who may be located far from the donor’s site. These typical scenarios naturally limit the number of successful transplantations.
As of 2022, there are currently over 100,000 people on the waiting list for an organ transplant in America with the average waiting time taking anywhere between four months to five years. According to The Spanish Transplant Organisation, there were approximately 49,000 patients on a transplant waitlist in Europe by the end of 2020, and only 28,000 transplant procedures took place. Approximately 21 people die every day in Europe waiting for a transplant. The unmet need for organ preservation places significant logistical limitations on transplantation and several other biomedical fields. The limited shelf life of biological tissues and cells not only hinders organ transplantation, but tissue engineering, drug discovery, and more.
Today’s Technology
Static Cold Storage
Since the 1960s, Static Cold Storage (SCS) has gradually become the gold standard method for organ preservation. SCS involves flushing the organ with a preservation solution at 0–4 °C, then immersing it into a solution at the same temperature until the transplantation. This hypothermic environment decreases cellular metabolism, and the preservation solution provides cryoprotection. SCS offers a simple and effective way to preserve and transport organs, however, a number of limitations are associated with it. Limitations include tissue damage, difficulty in assessing donor organ function and viability, ischemia-reperfusion injury (IRI), and limited organ repair possibilities. Despite SCS being the standard for organ preservation, it can only preserve organs and tissue for a few hours, making it an extremely short-term solution.
Machine Perfusion
Machine perfusion suggests another way to improve and prolong organ and tissue preservation outside of the body—or ‘ex vivo’. Hypo- and normothermic perfusion are available for the heart, lungs, livers, and kidneys. The hypothermic approach focuses on slowing down metabolic rates. Normothermic attempts to generate an ‘ex vivo’ environment by mimicking physiological ‘in vivo’ (inside the body) conditions. Systems are oxygenated and use either preservation solutions or diluted blood as perfusate. The first clinical attempts at machine perfusion were made in the 1960s but they failed to prove superior to SCS. However, over the years, and because of organ shortage, the strategy was re-introduced.
Vitrification
Vitrification is a method where organs and tissues are cooled to cryogenic temperatures with little to no ice crystal formation. The lack of ice formation is due to the addition of different cryoprotectants at a rapid and highly controlled cooling rate. The organs and tissues enter an amorphous glass-like state at around -125°C, allowing for virtually indefinite preservation, which is a necessity for organ banking. Successful cryopreservation using vitrification has, to date, largely been achieved in ovum (egg cells) and sperm, which can be cooled and rewarmed quickly. The only successful vitrification and subsequent transplantation of an organ was a rabbit kidney. Today, challenges with vitrification involve the potential toxicity of cryoprotective agents and obstacles with the rewarming process. New strategies are currently being developed to optimize this procedure.
Techniques for successful preservation at cryogenic temperatures have been developed over the past five decades for several tissue types, with some dramatic advances being made in recent times. Currently, however, successful applications are generally related to small specimens, ranging from stem cells to tissues, such as corneas. In humans, researchers have been able to cryopreserve larger specimens for tissues such as heart valves where the mechanical function is of higher priority than the biological function.
To advance the science and technology of cryopreservation, researchers are utilizing engineering concepts, including heat and mass transfer, solid mechanics, materials science, nanotechnology, computer modeling, information technology, and microelectronics. The engineering approach can integrate predictive tools that are rooted in physical measurements, mathematical modeling, and computation power, which could hugely benefit current and future research.
The Medical Need for Cryopreservation
Vitrification and Organ Banks
It is estimated that about two-thirds of potential donor hearts are discarded worldwide. Moreover, up to 20% of potential donor kidneys are wasted in the USA because of time constraints in finding suitable recipients. According to findings in the UK, discard rates of kidneys range from 10-12% and about 50% of pancreases. This waste could be avoided by advancing preservation methods, particularly cryopreservation, which is currently the only long-term preserving solution, in order to open organ banks around the world.
In addition to their role in helping to address organ shortage, advances in organ banking could greatly expand options for donor-recipient matching; enhance screening for transmissible diseases; decrease costs; enable a more flexible surgery scheduling, and assess organ quality before transplantation.
In 2017, Harvard Medical School organized the ‘Organ Banking Summit’ to discuss the current challenges facing cryobanking today. Leading scientists and engineers in the field came together to prepare a roadmap to overcome scientific hurdles in cryopreservation, which include:
- Control excessive ice formation
- Hold cryoprotectant toxicity at acceptable levels
- Limit disproportionate mechanical and/or thermodynamic stress
- Control excessive injury from chilling
- Avoid unacceptable levels of ischemic injury
- Ensure acceptable repair and revival protocols
As was stated at the symposium: to date, there are no effective methods to reliably preserve solid organs beyond 12 hours, but just a few hours of additional preservation time would greatly increase the number of possible transplantations globally.
Conclusion
Each year, 4,000 healthy organs are discarded because a match can't be found in time, while over 6,000 people on the waiting list die. Prolonging organ viability would allow transportation to wider geographical areas, making for accessible surgeries across the globe. Scientists say the gap between current and future technology needed for cryopreservation can only be bridged between cryobiologists and engineers working together. Presently, most research is only in its infancy, and applications and methods have only been tested on animals or basic human cells. Through further research, countless areas of public health could be revolutionized. Advancements in organ banks, oncofertility, tissue engineering, trauma medicine, emergency preparedness, and drug discovery could all be possible with better cryopreservation techniques.
Cryo experts at Tomorrow Bio are continually trying to advance biostasis research. Successes in the field of human cryopreservation work hand in hand with organ cryogenic research, influencing insights, developments, and achievements. Tomorrow Bio’s partner EBF has a biostasis lab where researchers are working to improve biopreservation techniques. Presently, EBF is home to a long-term storage facility for Tomorrow Bio’s cryopreserved patients. Moreover, exciting research happening at EBF ranges from optimization of cryopreservation protocols to intermediate temperature storage, which could prove transformative for organ transplantations.
If you want to learn more about human cryopreservation click here or if you’d like to support the research happening at Tomorrow Bio and EBF, just take a look at our Tomorrow Fellow Program. By signing up as a fellow you can support research, get exclusive perks, and save up for future cryopreservation.
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