Importance Score: 75 / 100 🔴
Groundbreaking Frozen Kidney Transplant Experiment Offers Hope for Organ Availability
In a significant step forward for organ transplantation, surgeons at Massachusetts General Hospital conducted a novel procedure at the end of March, aiming to revolutionize kidney transplants. The pioneering surgery involved implanting a frozen kidney into an animal, potentially resolving critical challenges in organ preservation and accessibility.
Experimental Procedure on Pig
The patient undergoing this innovative procedure wasn’t human, but a pig under anesthesia. The animal, requiring a kidney transplant, received an organ that had been cryopreserved for an extended period. Unlike typical kidney transplants which demand immediate implantation within a day or two, this frozen kidney had been removed and stored for ten days before being carefully thawed on the morning of the operation.
This marked an unprecedented attempt to transplant a previously frozen organ into a large animal, a procedure fraught with potential complications and uncertainties.
Optimism and Challenges in Organ Freezing
“I estimate the probability of success to be around 50 percent,” stated Dr. Korkut Uygun, a surgery professor and lead investigator, prior to the operation. Dr. Uygun also serves on the scientific advisory board of Sylvatica Biotech Inc., a company specializing in organ preservation through advanced freezing techniques.
The potential benefits of effectively freezing and storing organs are substantial and address a critical need in healthcare.
vCard.red is a free platform for creating a mobile-friendly digital business cards. You can easily create a vCard and generate a QR code for it, allowing others to scan and save your contact details instantly.
The platform allows you to display contact information, social media links, services, and products all in one shareable link. Optional features include appointment scheduling, WhatsApp-based storefronts, media galleries, and custom design options.
Addressing the Critical Organ Shortage
The demand for kidney transplants significantly outweighs the available supply. Over 92,000 individuals are currently on waiting lists, struggling with a severe and persistent organ shortage. The narrow window for viable transplantation, typically 24 to 36 hours post-removal, significantly limits the number of suitable matches and exacerbates this scarcity.
The prospect of establishing banks of stored, frozen organs could transform organ transplantation into a more accessible and elective procedure, a long-held aspiration within the transplant surgery field.
Historical Hurdles in Organ Cryopreservation
However, past efforts by medical scientists to freeze organs have consistently faced obstacles. Formation of damaging ice crystals was a common issue, destroying delicate organ structures. Furthermore, cryoprotectants, substances designed to prevent ice crystal formation, often proved toxic to cells. In other instances, frozen organs became excessively fragile and prone to cracking.
The Thawing Conundrum
Dr. John Bischof, a cryobiology expert at the University of Minnesota, although not involved in this particular pig kidney transplant project, highlighted another significant challenge: the complexity of thawing frozen organs. Even when the freezing process appeared successful, the subsequent thawing phase presented considerable difficulties.
Preventing Ice Crystal Growth During Rewarming
During organ freezing, researchers focused on minimizing ice crystal size to limit cellular damage. However, these microscopic crystals tended to enlarge during the warming process, causing significant harm to delicate cellular components. According to Dr. Bischof, “It’s a race against the expanding ice crystals during rewarming.”
He elaborated, “The crucial realization was that uniform internal heating is essential. Simply warming the organ’s exterior leads to temperature disparities between the edge and core, inducing stress and fracturing, similar to a cracked ice cube in a warm drink. Uniform and internal heating is the key.”
Dr. Erik Finger, a transplant surgeon and colleague of Dr. Bischof at the University of Minnesota, who also had no role in the Massachusetts General experiment, explained that while controlled slow freezing is necessary to prevent initial ice damage, rapid rewarming – 10 to 100 times faster than cooling – is crucial for successful thawing.
Through iterative experimentation, researchers refined their protocols, ultimately achieving success in freezing, thawing, and transplanting rat kidneys.
Scaling Challenges to Larger Organisms
However, transitioning to larger animal models introduced new complexities. “For forty years, rewarming was the primary obstacle,” Dr. Finger noted. “But with increased organ size, cooling itself becomes a significant challenge.” Cryoprotectants effective for small rat organs proved inadequate for larger organs.
Inspired by Nature: Lessons from Wood Frogs
At Massachusetts General, researchers explored an alternative strategy inspired by nature. Dr. Shannon Tessier, formerly a postdoctoral fellow in Dr. Uygun’s lab and now an associate professor of surgery at Harvard Medical School, who also holds an advisory role at Sylvatica Biotech and has a patent application related to the surgical method, drew inspiration from Canadian wood frogs. These amphibians possess a remarkable ability to survive freezing temperatures through a natural process of cryopreservation.
As temperatures drop, wood frogs undergo metabolic changes, enabling them to literally freeze solid. Cellular activity ceases, and their hearts stop beating. They enter a state of suspended animation, appearing essentially lifeless.
In this frozen state, the frogs become extremely brittle. “They can be fragile, you could accidentally snap off a limb if handling them too carelessly,” remarked McLean Taggart, a lab technician.
According to Mr. Taggart, “Dr. Tessier proposed, ‘Could we potentially adapt this natural process to preserve human organs?’”
Mimicking Nature for Organ Preservation
This question spurred research into the wood frog’s unique freezing adaptation. Prior to hibernation, wood frogs produce substantial amounts of glucose, which accumulates within their cells. This intracellular glucose lowers the freezing point of water inside the cells, preventing ice crystal formation.
The crucial question remained: could a similar approach be effective for warm-blooded mammals and their organs?
Remarkably, the answer was yes. Arctic squirrels, another mammal, employ a comparable mechanism to supercool themselves in frigid temperatures. Their cells reach sub-freezing temperatures, chilled but not frozen, preventing ice formation and drastically slowing metabolism, enabling them to survive without food.
Building on prior research, the Mass General team began working with freshly extracted, living rat livers, aiming to replicate the wood frog’s natural cryopreservation strategy. Their approach involved chilling the organs sufficiently to halt metabolic processes, but avoiding temperatures that would induce damaging ice crystal formation.
Developing a Novel Cryopreservation Solution
Their process commenced by infusing an artificial, non-metabolizable glucose into the organs. This synthetic sugar accumulates within cells, inducing a state of suspended animation by pausing metabolic activity. Concurrently, a dilute antifreeze, propylene glycol, is introduced to replace water within the cells. This dual action minimizes intracellular ice formation, the primary source of freezing-related organ damage.
Their innovative organ preservation solution comprises a mixture of dilute propylene glycol, artificial sugar, and Snomax, a compound used in artificial snow production. Snomax promotes the formation of uniform, minuscule ice crystals, minimizing potential damage from ice formation.
To thaw the frozen organs, the researchers reversed the process, immersing the livers in a warm solution containing propylene glycol and artificial glucose. The concentrations of these chemicals were gradually reduced until completely removed.
The researchers noted that perfecting this complex procedure required approximately five years of rigorous experimentation and refinement.
The subsequent phase involved scaling up the process to larger mammal species, specifically targeting pig kidneys for freezing and thawing experiments.
Ambitious Goals: Organ Banking and Xenotransplantation
Their long-term objective is ambitious: establishing banks of frozen pig kidneys, genetically modified for potential transplantation into human recipients. Xenotransplantation, the transplantation of organs from animals to humans, is a rapidly evolving field.
Other transplant surgeons at Massachusetts General Hospital are already exploring xenotransplantation using genetically modified pig kidneys. These kidneys have been transplanted into several human patients, with varied success rates. Recently, a patient who received a pig kidney that functioned for a record 130 days experienced rejection, necessitating organ removal.
Successful Pig Kidney Transplant
The success of Dr. Uygun’s team’s approach remained uncertain. “The current protocol was specifically developed for livers,” Dr. Uygun explained. “We were unsure if it would be effective for kidneys.”
However, the experiment yielded positive results.
The research team rigorously tested their methodology, freezing and thawing thirty pig kidneys to assess organ viability post-cryopreservation. They confirmed that kidneys could be stored frozen for up to one month without apparent degradation.
Verification of Kidney Function Post-Transplant
The critical question then became: would a previously frozen kidney function effectively after transplantation into a living organism?
In the March trial, a kidney frozen for ten days was selected for autotransplantation – transplanted back into the same pig from which it was harvested.
The thawing process commenced at 3 a.m., lasting two hours.
At 9 a.m., Drs. Alban Longchamp and Tatsuo Kawai, transplant surgeons at Mass General, surgically prepared the pig’s abdomen for implantation.
At 10:30 a.m., the frozen-thawed kidney was successfully implanted.
The pale organ rapidly transitioned to a healthy pink hue as blood circulation was restored.
Ultimately, the experiment was a resounding success. Prior to surgical closure, the researchers observed the crucial sign of functionality: the transplanted kidney produced urine, demonstrating the viability of their groundbreaking frozen organ transplantation technique.