Colleen Pietras explores the future of organ transplantation, from xenotransplantation to cryopreservation breakthroughs.
Organ transplantation is a highly advanced yet challenging field of medicine. For patients with end-stage organ disease, such as heart, kidney or liver failure, transplants offer the only viable option for longer, happier and healthier lives.
Since the first successful kidney transplant in 1954, advances in surgical techniques, immunosuppressive drugs and preservation methods have revolutionized the field of transplantation, enabling better outcomes and a growing global network of transplant programs.
However, even with the remarkable strides made in improving patient outcomes over the last half century, several complex issues remain, particularly around storage and preservation.
The issue of organ shortage
One of the more significant issues in recent years is the shortage of available organs relative to the number of patients on waiting lists. According to the Organ Procurement and Transplantation Network, in 2023, over 46,000 transplants were performed [1]. Still, over 103,000 men, women and children are waiting for an organ.
A common practice to address the organ shortage has been living or deceased organ donation. Living donation has become a safe practice due to advancements in surgical techniques. Living donation reduces waiting times and improves outcomes for recipients, particularly for those needing kidneys or liver segments where a matched living donor can be found. Deceased donation occurs after death and remains essential as the heart and lungs cannot be donated by living donors.
Xenotransplantation, or transplants with animal organs, has been positioned as a potential solution to the shortage of human organs for transplant. Aside from the potential immune response and risks of transmitting unknown microbes to the recipient, there are, in fact, a few potential advantages over allotransplantation, or transplantation of organs between the same species. Xenotransplantation could provide a virtually unlimited organ source while reducing infection risks from certain devastating viruses. Pre-screening animals and controlling their exposure to potential infections lowers the risk of infection to the human recipient. Additionally, some animal species are resistant to Hepatitis B and human immunodeficiency virus (HIV), which can be devastating to patients on immunosuppressive therapy.
Recent cases of xenotransplantation have shown early promise, and the discussion has extended into bioengineered organs that could assist in organ shortage crises.
Advances in regenerative medicine and stem cell technology boost the evidence behind genetically modified organs. Lab-grown tissues could provide healthier, better-matched organs with longevity and fewer immunologic challenges. Despite encouraging evidence to reduce or eliminate the need for traditional organs, ethical and technical challenges remain.
The next generation of concepts aimed at enhancing longevity and extending lifespan represents a convergence of several biomedical technologies. Full-body repair using engineered tissues, organs and replacement parts would incorporate bio-fabrication and 3D printing, scaffold technologies and gene editing tools that would address genetic predispositions to disease.
Prosthetic and synthetic organs as artificial replacements for organs such as the heart, lungs, or kidneys would reduce reliance on donor organs. Engineered replacements can mitigate age-related organ failure, a major factor in human mortality. They may additionally offer improved resilience to environmental stressors and biological damage, further extending healthspan.
Cryopreservation is indispensable for enabling these technologies to scale, ensuring availability during specific times of need. Combining engineered tissues and cryopreservation allows for routine maintenance of aging bodies by replacing or rejuvenating failing organ systems. Early intervention with cryopreserved and engineered tissues can prevent diseases such as cancer, cardiovascular conditions and neurodegenerative disorders.
Extending lifespan with transplants
Organ shortage is a global crisis, with the World Health Organization (WHO) estimating that the global organ supply is less than 10% of the worldwide need. Prolonging organ viability offers immense potential for healthcare by addressing a number of critical challenges. A notable benefit of this change would be the ability to redefine the timeline of what would be considered a viable organ.
Advances in preserving organs outside of the body with ex vivo perfusion allow for improved organ quality at the time of the transplant, increasing initial success rates and potentially extending the functional life of the transplanted organ. What if there was a molecule that allowed a donor organ to hibernate in suspended form until it was needed?
One cutting-edge biotechnology company is advancing organ preservation and regenerative medicine with the hope of eliminating organ transplant waiting lists altogether. X-Therma, founded in the San Francisco Bay Area in 2014 by Dr Xiaoxi Wei, CEO, and Dr Mark Kline, CTO, is championing the transformative movement from small molecules to biologics and cell therapy with the knowledge that a cryopreservation medium is required to protect and extend the shelf-life of living cells, tissues and organs.
The science of cryopreservation
Preservation of living cells and tissues and transporting organs from one location to another is as common a concern as is the replacement of the same with new body repair technologies and current and future cell therapies intended to cure various diseases. All require the use of extremely low temperatures, or cryopreservation, to maintain their structural integrity. One of the main challenges associated with cryopreservation is the formation of crystals that can permanently damage the cells. To impede damage during the freezing process, a cryoprotective agent (CPA) is incorporated into the solution. One of the most commonly used CPAs today, dimethyl sulfoxide (DMSO), is effective for some cell preservation but toxic at high concentrations, making it unsuitable for organ transplants.
Enter peptoids.
X-Therma began by investigating the properties of nature’s most advanced antifreeze. Observations of various aquatic species’ unique ability to survive at sub-zero temperatures led researchers to examine antifreeze proteins (AFPs) in small animal organ transplants. However, the properties of the natural AFPs (easily degraded, unstable, low quantity, etc.) make their use impractical in a clinical setting to preserve organs. By using biomimetic nanoscience, X-Therma developed a novel molecule, or “peptoid,” mimicking the function of the proteins found in nature.
X-Therma’s biomimetic peptoid has the ability to prevent recrystallization while maintaining functionality and viability during significant temperature variations (below 0 degrees Celsius) and is now a key component of the company’s next-generation cryopreservation solution, XT-ViVo®.
Redefining organ transplantation
X-Therma’s technology demonstrates the potential to overcome storage limitations in order to extend preservation times beyond the current standards (i.e., 24 hours for kidneys moved to 5 days, 4 hours for hearts perhaps up to 24 hours). This would increase the donor pool, allowing geographically distant organs to be a dependable option.
Halting biological activity would allow more time to find the best matches for patients and improve transplantation logistics, such as reducing organ waste by creating an organ bank, where organs can be stored and used when needed. Extended storage enables better donor-recipient matching, reducing rejection risk and improving survival rates.
Extended preservation would allow patients from anywhere in the world to have the chance to receive a compatible organ. For patients requiring multiple organ transplants, cryopreservation ensures all compatible organs are available simultaneously for a coordinated procedure. For medical professionals, there would be more time to prepare for surgeries, reducing complications, enhancing operating room operations and improving outcomes for both donor and recipient.
The journey toward advancing organ transplantation and longevity involves breakthroughs in immunosuppressive therapies, regenerative medicine and biotechnology. Organ transplantation has moved beyond life-saving strategies toward fostering long-term health and longevity. The synergy of tissue engineering, advanced concepts in organ transplantation, and cryopreservation has transformative potential that will require interdisciplinary collaboration, innovation in cryobiology and careful navigation of the associated ethical and societal implications. With the right medical advancements and supportive care, future transplant recipients could achieve lifespans approaching those of the general population.
About Colleen Pietras
Colleen Pietras, MD, is a cardiac surgeon, most recently as an assistant professor at Yale University School of Medicine. She was trained in cardiothoracic surgery at Penn State Milton S Hershey Medical Center, advanced cardiovascular surgery at Mayo Clinic Rochester, and in heart and lung transplantation at the Hospital of the University of Pennsylvania. She has been published in the Annals of Thoracic Surgery and was part of a collaborative book chapter about End-Stage Heart Failure and Mechanical Circulatory Support. She has been a reviewer for the Journal of Heart and Lung Transplantation and the American Society for Artificial Internal Organs.
Dr Pietras earned her Bachelor’s in Biology/Pre-Med from Russell Sage College in New York and a Master’s in Physiology from Boston University before earning her MD at the Medical University of the Americas.
[1] https://unos.org/transplant/
