Every year, tens of thousands of Americans wait in what they call "medical purgatory" for an organ transplant. In 2018 there were more than 36,529 organ transplants, a number that has risen by 20 percent over the last five years. However, there are far more sick patients waiting on the transplant list — about 114,000 total, according to data from United Network for Organ Sharing (UNOS), which serves as the national Organ Procurement and Transplantation Network under federal contract. That's why an average of 8,000 people die every year waiting for the organs they need.
Now researchers, doctors and policymakers are exploring new strategies to increase the supply of organs needed to meet demand. Among the promising pursuits: advancing stem cell research in an effort to heal damaged organ tissue; developing biofabrication techniques in an effort to fast-track the 3D manufacturing of human organs, and using gene-editing techniques to find safe ways to use pig organs for human transplants.
The coordinated movement comes at a time of crisis in America. Rising obesity and diabetes rates is taking a toll on the human body. It is increasing the incidence of kidney disease and a form of fatty liver disease known as nonalcoholic steatohepatitis (NASH). These conditions typically lead to kidney and liver failure in people as young as 30. Even the pediatric population has been affected. For these individuals an organ transplant is their last hope.
"Recognizing the trend, UNOS is looking for ways to widen the donor pool and improve the way organs are allocated for transplantation nationwide," said Dr. David Klassen, UNOS' chief medical officer.
Right now it is rewriting distribution algorithms to improve the access of organs geographically. It is also exploring ways that would let transplant centers accept organ donations more quickly.
One strategy being used to address the immediate need is the use of living donors. Last year 19 percent of all transplant surgeries in the United States were from living donors, the highest in 12 years, reports UNOS. In these surgeries donors give a portion of an organ (i.e. liver) or an entire organ such as a kidney to another person whose organ is no longer functioning properly.
Another is broadening the set of medical criteria for organ donations. For example, now hospitals are using livers that are infected with the hepatitis C virus in transplants and then curing patients of the disease with new drugs — i.e. Harvoni, AbbVie and Sovaldi — after surgery. There is even a UNOS-approved program at Johns Hopkins Comprehensive Transplant Center that transplants organs, such as livers and kidneys, from living donors infected with HIV to patients who already have the virus.
Stepping up to the challenge, "a number of tech companies are working on devices and processes to better preserve and transport organs," said Elling Eidbo, CEO of the Association of Organ Procurement Organizations. As he explained, this is vitally important since many organs — especially lungs and hearts — get damaged or die in transport because of lack of blood supply, time limitations and geographical logistical challenges.
One company that has received FDA approval for a breakthrough device is TransMedics. The company received FDA approval in March for its Organ Care Lung System, the first portable device that maintains lungs in a near-physiologic state outside the body, addressing the limitations of cold storage used today. The machine is designed to replicate human functions as closely as possible so organs can be preserved for a longer period of time.
The process involves attaching the donated lungs to a ventilator, pump and filters. The lungs are maintained at normal body temperature and treated with a solution that contains nutrients, proteins and oxygen, which can reverse lung injury. The technology is being used especially to preserve lungs and hearts that typically have only up to six hours after recovery for use.
OrganOx, a U.K. start-up, has developed a similar machine that is being used to transport livers. The machine called the OrganOx metra device, maintains a liver's normal body temperature and delivers oxygenated blood, anti-clotting drugs and nutrients to the organ for up to 24 hours. In a recent study funded by the European Commission, the device was used across seven European transplant centers and was shown to reduce tissue injury and improve quality assessment of organs prior to surgery.
The metra machine is a breakthrough since it allows doctors to monitor liver performance in real-time by providing continuous data on such parameters as blood flow, bile production and lactate clearance. In the future, the technology can open the door to further treatment of donor organs, since a longer transplant window could make time for drug or stem cell-based treatments.
"The goal is to double the number of livers that can be used for transplants," said Dr. Constantin Coussios, co-founder of OrganOx and professor of biomedical engineering at the University of Oxford. The device that has won regulatory approval in Europe, India, Australia and Canada is now being tested in the U.S. in 15 transplant centers. Dr. Coussios hopes to get FDA approval by 2020 for usage of the machine in the United States.
"It offers a way for doctors to test-drive an organ and reduce uncertainty about its viability for a patient," Dr. Coussios explained. "It also gives the surgeon more time to find the appropriate recipient and plan surgeries. This reduces risk."
Recognizing how perfusion technology can help in organ assessment and repair before transplant surgery, the Mayo Clinic in Jacksonville, Florida, has forged an agreement with United Therapeutics for them to equip and operate a lung restoration facility by year-end. The facility, called Lung Bioengineering, will use ex vivo lung perfusion machines to assess and treat donor lungs prior to transplant.
"We have already performed 11 lung transplants using this technology," said Dr. Burcin Taner, chairman of the department of transplantation at the Mayo Clinic in Jacksonville. "In the past, many of these organs would have been deemed unusable organs because of edema, infection and other reasons. This is a great way to boost organ resources and do surgeries earlier, before patients become too sick for a transplant. It will service our center and other transplant centers in the Southeast."
The organizations also plan to work together on regenerative medicine research — a game-changing field with the potential to heal damaged tissues and organs.
For two years the Mayo Clinic has been doing stem cell research to treat a host of conditions, including blood cancers. Now it is exploring ways to use stem cells to heal the brain after a hemorrhagic stroke and regenerate heart tissue and reduce transplant rejection.
Dr. Tushar Patel, dean of research at the Mayo Clinic, is pioneering a new kind of therapy that can be used for the repair and regeneration of organs. He has been exploring how nanoparticles known as extracellular vesicles (EVs) obtained from stem cells can be bioengineered to help in tissue repair.
"EVs are routinely released from cells and play a central role in cell communication, sharing vital information such as RNA and proteins. We are looking at how the human body can use EV from stem cells to assist in tissue repair. This could create a whole new generation of cell-free therapies," said Patel.
Looking toward the future, scientists are working on breakthroughs that would have been unimaginable a decade ago.
One of the most promising areas is the field of xenotransplantation, or cross-species organ transplants. "We are only one or two years away from clinical trials of modified kidney transplants from genetically modified pig models to humans," said UNOS' Dr. Klassen.
Xenotransplantation is not entirely novel. Pig heart valves have been used for many years without ill effect and seldom elicit rejection. Some scientists believe whole organ transplants from genetically modified pigs are possible in the near future if immunological and physiological barriers can be overcome. The reason they are targeting this quick-breeding species is because they are anatomically similar to humans and can be gestated and grown for transplant in a relatively short period: six months.
Their goal is to create a future in which designer swine, raised in pathogen-free indoor farms, will serve as spare parts factories for ailing human bodies.
A pioneer in this field is Dr. Joseph Tector, a surgeon-scientist and director of the University of Alabama at Birmingham's Xenotransplant Program. He is busy trying to crack the code on how to place pig organs in human bodies. His goal is to overcome immune-system incompatibility and minimize rejection risk by using CRISPR gene-editing techniques to knock out any sugars on the surface of pig cells that will be attacked by human antibodies if the organs are transplanted into human patients. While a biotech start-up eGenesis is also developing technology in this field, Tector says his model is different in that it involves less gene editing of the genome.
"We want to do as little gene editing as possible to reduce risk," Dr. Tector said. He explained that CRISPR gene editing can be imprecise, and sometimes it can clip DNA in the wrong spot, potentially wiping out tumor-suppression genes in pig donors or human recipients. "The last thing we want is to suppress the immune system so much that it cannot fight infection."
Why is he dedicated to this approach? "There has been a been a lot of rationing of human organs for transplant but that just determines who lives or who dies," Dr. Tector says. "As the population grows we need new sources to meet demand."
Another strategy is to advance human organ and tissue manufacturing. This is the next frontier of medicine. Biofabrication is already a real concept getting close to market.
One company that is helping to turn this lofty goal into an eventual reality is Cellink. The Swedish-based start-up listed on the Nasdaq exchange claims it is the first bioink company in the world. It has created several different varieties of bioink — materials that mimic the natural environment that cells grow in, and which can be mixed with living cells to create functional human tissues with a 3D printer.
The company has created the first community in the bioprinting field that includes 500 universities in 50 countries. "The end goal is to enable organ printers in the future so these vital organs can be manufactured and transplanted," said Cellink's founder and CEO, Erik Gatenholm. "Our hope is that it can be a reality in 10 to 15 years."