Extra time

An engineering and transplant expert trio is leading an effort to extend current time
and possibly transform the science of transplantation. Researchers hope to develop a
working prototype of their so-called bioreactor in five years

When someone’s body parts are donated, it’s a life-or-death race against the clock as hearts, lungs, livers and hands rapidly deteriorate outside the body.
A trio of engineering and transplant experts from the University of Maryland, Baltimore County and Johns Hopkins University are leading an effort to extend that time and possibly transform the science of transplantation.
“When you take organs from a natural environment to a man-made one, survival time is short,” said Gymama Slaughter, a computer science and electrical engineering associate professor at UMBC. “What if we could buy time to save someone’s life?”
Typically organs last as little as two hours and as long as 36 hours once they are removed from the body. The researchers’ approach involves better managing the environment body parts are stored and transported in to possibly extend the window to 72 hours or longer.
The US Army Medical Research and Material Command is funding the project through a three-year, $1.5 million grant. The US military often pays for medical research that can benefit service members, veterans and eventually everyone else.
The researchers hope to develop a working prototype of their so-called bioreactor in five years.
Their plan starts with the same nutrient-infused solution used now to preserve an organ in a container once it’s taken from a body. The container is kept chilled on ice for transport.
The researchers are developing a sensor array to monitor the solution for levels of nitric oxide, lactic acid, glucose and free radicals that indicate deterioration of the organs. The solution could then be tweaked to reduce or slow the body parts’ degradation. Other measures could be added later to improve the organs’ functioning.
Preserving body parts longer would give transplant professionals more time to better match organs and recipients in a larger geographer area, and create less waste, experts said.
There are more than 116,500 people on the organ transplant waiting list, according to the United Network for Organ Sharing, the nonprofit that manages the transplant system.
Figures provided by UNOS show that there were 31,917 organs recovered in 2016 for transplant and 27,540 were transplanted. Some 4,377, or close to 14 percent, were discarded for various reasons including time, though more often because of test results showed they were unusable.
Dr David Klassen, chief medical officer for UNOS, said there is a computer program for allocation that varies slightly by organ and considers time. Kidneys, the most commonly transplanted organ, last the longest and usually can even be flown across the country. That allows more flexibility and time to consider issues such as medical compatibility, he said.
Hearts and lungs have four to six hours and typically don’t travel far. Livers have only a bit longer and also typically go to the sickest person nearby.
Transplant experts say a hand or face — called vascularised composite allotransplantation, or VCA — has as little as a couple of hours and offers from donor families have been refused because of the limitations.
“There are many people working on improving the technology” that would extend time, Klassen said. “These efforts are very, very important and will shape allocation policies going forward. … There are now some organs procured for transplant, but time runs out before an acceptable recipient can be found.”
There are hurdles beyond medical, however. The National Academy of Science released a report last week that looked at the ethical and legal issues related or organ research. The report said such research is necessary to improve the rate of transplantation and the quality of organs.
The report aimed to address basics such as whether studying organs from deceased donors constitutes “human research,” said Robert Veatch, a professor emeritus of medical ethics from Georgetown University’s Kennedy School of Ethics who has participated in an academy meetings on the subject. Human research triggers federal reviews.
At the centre of the debate, however, has been consent, he said. Donors and recipients would need to specifically approve of organs that had been altered somehow. Recipients also might need to consent to monitoring to determine how organs fare.
“The recipients will be receiving a manipulated organ that may have been harmed as well as helped by the manipulation,” Veatch said. “Even if they do not have a right to consent to receiving the organ, surely they have a right to consent to having their records accessed to study the result.”
Among the report’s suggestions were creation of a national registry, rather than state or regional ones, to communicate donor preferences and a central research repository to keep the public informed.
It also suggested donors could consent to organ research at the same time they agree to donation, on their drivers’ licences for example, so long as effective educational materials can be developed. Recipients could consent in principle when they are listed for a transplant and then again once a specific organ becomes available.
Warren Grayson, an associate professor of biomedical engineering at Hopkins, said such issues were not a factor in their research grant application.
“There is a recognised need for technologies to better preserve organs and so there is more funding becoming available in this area,” he said. “Donors-donor families provide consent to donate their organs-tissues, so there is no need to obtain consent for preserving the tissues so that they can actually be used. This is not so much manipulation as much as just preservation.”
For the next three years under the grant, the researchers also will not use human organs or tissue. They will use the abdominal wall of a rat.
Eventually, they plan to test the bioreactor system on human body parts. The researchers expect it would work for all kinds of organs, though the military’s interest is specifically in better preserving body parts such as hands for the complicated VCAs. Such transplant procedures — involving muscle, bone and tissues — are mostly used on patients with a severe injury such as those sustained in combat or by accident.
The Defense Department created the Reconstructive Transplant Research Program in 2012 to advance the science of VCA procedures and has granted more than $8 million to a dozen projects to extend the time for transplantation.
Trish Henry, programme manager for this military research effort, said extending that window “would greatly increase the feasible physical distance, thereby increasing the chances of finding an appropriate donor-recipient match.”
She said another possibility from improving the technology is preserving a patients’ own damaged tissue for late use in reconstruction.
The ability to preserve — and someday maybe even improve — organs means more could be harvested and used, reducing the backlog of patients on the transplant waiting list, said Dr Gerald Brandacher, scientific director of the Reconstructive Transplantation Program in Hopkins’ School of Medicine and a hand transplant expert.
The bioreactor’s constant monitoring of the organs might make transplants safer for patients, said Brandacher, the third member on the research project. Organs now are cooled and unmonitored until they are transplanted.
The system also can help overcome other obstacles, he said. In the case of hands, for example, an electric current could be applied to keep muscles moving and in good working order.
More time for transplantation could allow for better matching of VCAs for size, gender and skin colour. The extended window also would allow tolerance building in recipients so they might need fewer harsh drugs to suppress their immune systems and prevent organ rejection, a major goal in the transplant community, Brandacher said.
Others who are not good candidates for transplantation could be given another chance by desensitising them to organ-rejecting antibodies they’ve developed through past blood transfusions or transplants.
Brandacher said he believes the bioreactor system being developed by the researchers could be a crucial advancement, and faster to the gate than other projects underway — including another farther off in his lab to freeze and bank organs for later transplant.
“There are so many possibilities,” he said. “This could be the biggest game changer for transplants in the history of the field.” — The Baltimore Sun/TNS

TIME-OUT
Kidneys, the most commonly transplanted organ, last the longest and usually can even be flown across the country. That allows more flexibility and time to consider issues such as medical compatibility. Hearts and lungs have four to six hours and typically don’t travel far. Livers have only a bit longer and also typically go to the sickest person nearby. A hand or face has as little as a couple of hours