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X-Therma, a member of the Biotechnology Innovation Organization (BIO), is making significant headway in its fight to abolish the organ transplant list.
With X-Therma’s FDA breakthrough-designated subzero preservation technology, a pig kidney preserved at subzero temperatures was successfully transported across the Atlantic Ocean multiple times, setting the record as a world’s first. This milestone paves the way to make extended organ storage and long-distance transportation a clinical reality, said the company in an Oct. 23 announcement.
According to the United Network for Organ Sharing (UNOS) the number of patients awaiting an organ transplant in the United States surpassed 100,000 in 2023. Over 40,000 transplants are performed annually, and, despite immunosuppressive therapy, 20% of recipients experience at least one episode of rejection. In 2021, an estimated 20,000 deceased donor kidneys were procured for transplant, and more than 20% of them were discarded.
In a strategic effort to mitigate the consequence of an imbalance in organ supply and demand, X-Therma has invested time and resources to find a solution.
The science of cryopreservation
X-Therma, founded in the San Francisco Bay Area in 2014 by Dr. Xiaoxi Wei, PhD, CEO, and Dr. Mark Kline, PhD, CTO, is focused on the advancement of organ preservation and regenerative medicine. The company 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.
Preserving live cells and tissues and transporting live organs from one location to another requires cryopreservation, or using extremely low temperatures to maintain the structural integrity of a living cell or tissue. One of the main challenges associated with cryopreservation, however, is that freezing temperatures result in crystal formation, which damages cells and tissue. To try to impede damage during the freezing process, a cryoprotective agent (CPA) is incorporated into the solution to reduce the chances of injury-causing ice formation. One of the most used CPAs today is dimethyl sulfoxide (DMSO), which, though effective, is toxic at high concentrations and thus cannot preserve organs for transplant.
“Typical cryoprotectants work for cells but, given the dose needed to prevent freezer burn in organs, would be harmful,” explained Dr. Wei.
X-Therma’s peptoid technology
The research team at X-Therma began by investigating the properties of nature’s most advanced antifreeze. Their observation of a variety of aquatic species and their unique survival ability at sub-zero temperatures expanded into a review of 30 years of research on anti-freeze proteins (AFPs). By using biomimetic nanoscience, they developed a novel molecule, or “peptoid” resembling the structure and function of the proteins found in nature.
X-Therma’s biomimetic peptoid “has greater functionality and advantages compared to peptides seen in AFPs,” according to Dr. Wei. Due to its unique structure, its peptoid has the ability to prevent recrystallization while maintaining functionality and viability during significant temperature variations (below 0 degrees Celsius).
Put simply, X-Therma’s ice does not damage cells. In fact, evidence supports the assertion that X-Therma’s peptoid preserves cells and tissue more efficiently and effectively than AFPs.
In November 2023, Bio.News reported on X-Therma’s peptoid, a key component of XT-ViVo, the company’s next-generation cryopreservation solution. At low concentrations, XT-ViVo is a non-toxic, serum- and protein-free organ preservation solution and is capable of controlling ice formation, enabling ice-free preservation of organs between 0°C and -20°C.
Regulatory status and applications
The U.S. Food and Drug Administration (FDA) granted Breakthrough Device status to XT-ViVo® and TimeSeal® organ transplant device for human kidney preservation up to 120 hours for transplant in May of 2022.
Utilized in the flushing and perfusion process between donor and recipient, XT-ViVo prevents damaging ice crystal formation during organ preservation at sub-zero temperatures and can support a reduction in metabolism while warding off unwelcome injury. X-Therma’s TimeSeal device is a smart-sensored, portable transporter designed for static hypothermic preservation of adult donor kidneys while maintaining organ functionality and viability between clinical environments.
With the ability to be carried on a commercial aircraft, TimeSeal® allows for precise monitoring of temperature, storage duration, and location without requiring external power, blood, or oxygen.
The benefit of extending organ preservation time would bridge the gap between organ supply and demand, avoid high-risk, time-critical emergency surgeries, and potentially achieve advanced genetic matching, leading to more organ transplants. As described by Dr. Wei, X-Therma’s goal “is to minimize tissue damage and extend the time for organ transport. This will further increase the global availability of organs, which will expand the organ donor pool and improve donor-recipient matching.”
A world first in organ transport
Over the course of the past 12 months, Dr. Gerald Brandacher led a surgical team to remove a kidney from a pig at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and transport it on a commercial aircraft to the Medical University of Innsbruck in Austria. The kidneys were preserved in X-Therma’s XT-ViVo® solution in X-Therma’s TimeSeal® device. Preserved for roughly 48 hours at subzero temperatures, the kidney was assessed in Innsbruck on a clinical-grade machine perfusion device and demonstrated viability and functionality.
The team repeated the process five times, with preservation times ranging from 48-72 hours. As proof of concept of the technology, the team performed a life-supporting transplant in a pig, with the kidney maintaining normal renal function during the entire observation period for 200 days post-transplant after 72 hours ice-free subzero preservation.
Dr. Brandacher is Professor of Translational and Experimental Transplant Surgery, Co-Director and Executive Vice Chair for Research of the Department of Visceral, Transplant, and Thoracic Surgery, and Scientific Director of the Daniel Swarovski Transplantation Research Laboratory at Medical University of Innsbruck. He is also a professor in the Departments of Surgery and Plastic and Reconstructive Surgery at the Johns Hopkins University School of Medicine and Scientific Director of the reconstructive transplantation program. As one of X-Therma’s medical advisors, he has been closely involved in the research and implementation of both XT-ViVo and TimeSeal.
“XT-ViVo and TimeSeal are stream-lined, modifiable, and easy to use,” he explained. “The transporter does not require extra steps. It does not require external power, oxygen, or blood for the tissue or organ to survive and is trackable during transport for optimum temperature stability.”
The proof of concept has far exceeded his expectations, and, with specific tailoring, he expects a great future for X-Therma’s technology to fundamentally change the ways of organ preservation.
X-Therma technology demonstrates incredible potential to overcome storage limitations with no additional steps and no additional perfusion instrument, blood, or oxygen. By extending preservation times beyond current standards—24 hours for kidneys, 4 hours for hearts—the future of enhanced transplantation outcomes and open access to more transplants is now more realistic than ever.
“By dismantling the traditional barriers of distance and time, our technology heralds a transformative era in organ transplantation, potentially making organs more accessible and saving more lives,” said Dr. Wei. “With recent legislation permitting organ transport in commercial aircraft cabins, X-Therma is at the forefront of flexible global sharing of organs, tissues, and cells, with pioneering technology that seamlessly integrates into existing peri-transplant workflows and ensures time is on our side.”
The results utilizing X-Therma’s technology were presented to peers at several events, including by Dr. Brandacher on July 25, 2024, at the Society of Cryobiology’s 61st annual meeting in Bethesda, Maryland, and by Amanda Loftin, DVM, Ph.D. Candidate at the Johns Hopkins University School of Medicine, on September 25, 2024, at The Transplantation Society in Istanbul. Dr. Loftin’s presentation was selected as one of the TSS meeting’s top four abstracts in the United States. The results have been validated through extensive pre-clinical studies in various organ systems.
