NIH-funded research project develops new method to preserve human livers for transplantation
Scientists have greatly extended the amount of time human livers can be stored for transplantation by modifying a previous protocol to extend the viability of rat livers. Previously, human livers were only viable for an average of nine hours, but the new method of preservation maintains liver tissue for up to 27 hours, giving transplant doctors and patients a much longer timeframe to work with.
The research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), both part of the National Institutes of Health.
Like a glass container broken by frozen water, when cells freeze, they often experience irreparable damage. Since human cells are especially sensitive, donor livers are stored above freezing at 4 degrees Celsius. As a result, doctors can typically only preserve human livers for nine hours before the chances of a successful transplantation drastically decrease. This short time frame makes it more difficult, and sometimes impossible, to get the organs to compatible patients who are located farther away.
“Delivering viable organs to matching recipients within the window of viability can often be the most challenging aspect of organ transplantation,” said Seila Selimovic, Ph.D., director of NIBIB’s Engineered Tissues program. “By giving doctors and patients more time, this research could someday affect thousands of patients who are waiting for liver transplants.”
In previous studies funded by NIH, Martin Yarmush, Ph.D., director of the Center for Engineering in Medicine, Korkut Uygun, Ph.D., associate professor of surgery, and their collaborators at Massachusetts General Hospital (MGH), Boston, had developed new techniques that extended the time that rat liver (hepatic) tissue can be stored at subzero temperatures without damage. They were able to do this by adding a modified glucose compound, 3-OMG, and PEG-35kD—an ingredient in antifreeze—to the protective solution that they use to cool the livers. The PEG compound lowers the temperature at which the cells freeze and 3-OMG acts as a protectant against the cold. With these additions, they were able to cool the rat livers to 6 degrees Celsius without freezing them—a process called supercooling.
However, while the techniques worked with the rat livers in those earlier studies, it was unsuccessful when applied to human livers, which are 200 times larger. The size difference significantly increased the risk that ice crystals would start to spontaneously form (heterogenous ice nucleation), making the organ unusable for transplantation. In a paper published in Nature Biotechnology on Sept. 9, Reinier de Vries, M.D., a research fellow in surgery, Shannon Tessier, Ph.D., instructor in surgery at MGH and Harvard Medical School, Boston, and Uygun, and their collaborators at MGH detail three new steps to the protocol to avoid ice nucleation and preserve human livers for up to 27 hours.
“With supercooling, as the volume increases it becomes exponentially more difficult to prevent ice formation at sub-zero temperatures,” said de Vries. “Before, there were a lot of experts who said, ‘well this is amazing in small rats, but it will not work in human organs,’ and now we have successfully scaled it up 200 times from rat to human livers using a combination of technologies.”
The first step was to limit the contact of the storage liquid to air. When supercooled, the livers are submerged in the supercooling protective solution. The researchers found that the risk of ice crystals forming greatly increased in areas where the solution was in contact with air. To eliminate this risk, the scientists removed the air from the storage solution bag prior to supercooling, effectively eliminating the chance of spontaneous ice nucleation on the surface of the organ.
Next, the researchers included two additional ingredients to the protective solution to help protect the hepatocytes. The first additive, trehalose, helps to protect the cell as well as stabilize the cell membranes. The second, glycerol, supports the protective properties of the 3-OMG glucose compound added in the previous experiments. Both additives have been used in the cryogenic preservation of cells in the laboratory but had not been used in the preservation of organs for transplantation.
Finally, they developed a new method of delivering the preservation solution to the liver. The traditional method of delivery of the protective solution used in previous studies is to manually flush the preservation solution through the tissue. However, the new protective solution is thicker than the traditional solutions and can cause damage to the cell lining the inside of the blood vessels. In addition, the higher viscosity means that the solution is often not uniformly distributed throughout the organ, increasing the chance of ice nucleation spreading and freezing the liver. To combat this problem, the researchers used machine perfusion—a way of delivering oxygen and nutrients to capillaries in biological tissues while outside the body—at 4 degrees Celsius with the traditional protective solution. They then slowly lowered the temperature while increasing the concentration of the new protective additives. The staggered approach allowed the hepatic tissue time to adjust and the solution was able to spread throughout the organ more uniformly.
While the researchers have yet to implant a liver preserved using this new method into a human subject, traditional standards of assessing liver viability indicate that this process will not negatively affect the organ.
The Latest on: Organ transplantation
via Google News
The Latest on: Organ transplantation
- UGA researchers: Pediatric transplant patients skipping adult appointmentson May 2, 2022 at 11:20 am
ATHENS -- Young adults who received organ transplants as children may not be regularly attending their doctor appointments after leaving their pediatric providers. Missing these appointments is ...
- AYA Solid Organ Recipients Need Support After Transfer to Adult Careon May 2, 2022 at 11:18 am
MONDAY, May 2, 2022 (HealthDay News) -- Adolescent and young adult (AYA) solid organ transplant recipients should be supported after transfer to adult health care, with improved clinical outcomes ...
- Life After a Lung Transplant, During a Pandemicon May 2, 2022 at 10:39 am
So, when considering getting the COVID-19 vaccine or treatment, I was concerned about increasing the possibility of organ rejection. I decided to join the Johns Hopkins Transplant Vaccine Study Group.
- ‘Meaning and purpose’: Fairfield man an organ donor three times overon May 2, 2022 at 7:00 am
Anthony Cernera’s path to becoming an organ donor began with him trying to talk a friend out of donating a kidney. A few years ago, the 39-year-old Fairfield resident saw a Facebook post from a friend ...
- Pediatric transplant awareness week, organ donationon April 30, 2022 at 10:45 am
Finding an organ donor for kids is especially hard. Today is the end of pediatric transplant awareness week, which is a part of “donate life month”. 10-year-old Max Grau and his doctor, Dr. Islam ...
- Phillip Hanks celebrates his transplant-aversary with 5 new organson April 30, 2022 at 1:04 am
Hanks, a father of six, received a multivisceral transplant — a simultaneous transplant of multiple organs — at Indiana University Health in Indianapolis in April 2021. Since then, Hanks, of Joliet, ...
- Christ Hospital celebrates 50 years of kidney transplants as Organ Donation Month winds downon April 29, 2022 at 3:45 pm
April marks Organ Donation Month and to celebrate Christ Hospital is marking its 50th year of kidney transplants.
- 3 brothers, 2 transplants, a long wait for another heart: A family illustrates life-saving impact of organ donorson April 29, 2022 at 12:58 pm
Nearly 106,000 people in the U.S. are waiting for an organ transplant, and 17 people die each day while on the waitlist, according to the U.S. Health Resources & Services Administration. RELATED: YOUR ...
- First responders rush double organ transplant recipient to hospitalon April 27, 2022 at 7:31 pm
After a six month wait for a double organ transplant, Sara O’Daniels had to get to University Hospital within the hour to receive a kidney and liver transplant. NBC News’ Tom Llamas explains how ...
- How pediatric organ transplants can save lives and help kids be kids againon April 26, 2022 at 10:00 pm
Motta Law Firm is proud to honor and celebrate the gift of life provided through pediatric donation and transplant. April 24-30 is National Transplant Week for more information on how ...
via Bing News