Breakthroughs Fuel Organ Banking Summit

Organ transplants are a race against time. The clock starts ticking as soon as physicians harvest a heart, a kidney, or another organ. They have only a handful of hours to speed them to a hospital where surgical teams are waiting. If they miss their deadline, the organ and maybe the patient will die.

The Organ Banking Summit attracted more than 100 physicians, engineers, and scientists seeking to change that paradigm from a race into elective surgery that patients can schedule in advance by finding ways to preserve human organs for days, weeks, and even years at a time. The meeting was held this month in Boston, MA.

The stakes are high because the lack of viable transplants is a hidden killer. The true need for heart transplants is 10 times larger than the number of patients on the heart transplant list, according to a well-respected study by the International Society for Heart and Lung Transplantation's Xenotransplantation Advisory Committee in 2000. This is likely true for many deaths from end-stage organ diseases. They total 750,000 U.S. deaths annually, a number higher than the number of U.S. cancer deaths.

Organ banking would enable surgeons to pick organs that best match an individual patient, and to plan operations rather than throw together surgical teams at the last minute. Some researchers have shown that, with additional time, they can repair and improve damaged organs that we now throw away, or genetically modify organs (and patients) to reduce immune response. 

Over the past decade, researchers have taken enormous strides toward this brave new world. They have succeeded in preserving small organs and tissues, often by rapidly cooling samples to temperatures well below zero. This is called cryopreservation and is commonly used to preserve sperm, eggs, embryos, stem cells, blood products, some types of tissue, and heart valves.

Over the past few years, researchers have begun to work with larger samples. Now, they can cryopreserve ovarian tissue from women before they receive chemotherapy for cancer, then resuscitate the tissue and implant it so that those same women can give birth to healthy babies. Researchers have frozen and transplanted working rat hearts and hind limbs, and kept supercooled rat livers viable for three or four days.

The reason organs do not last longer is that water, which makes up about 60 percent of humans and other mammals, turns to ice when it freezes. As ice crystals expand they puncture cell membranes and can turn the delicate structure of a kidney to mush.

Researchers have found some ways around the problem. One approach is vitrification, which keeps water in a glassy solid state by perfusing the organ with cryoprotectants, which are mixtures of chemicals similar to antifreeze, and ice blockers, proteins or other materials that keep arctic animals from freezing.

While this prevents ice formation during freezing, reheating can cause thermal stresses that can crack a vitrified organ and make it useless. This is especially true for larger organs whose mass takes longer to reheat.

Twenty First Century Medicine, founded by vitrification pioneer Greg Fahy, was the first research team to vitrify, warm, and implant a functioning rabbit kidney in 2009. His team has reduced ice formation to 0.5 percent from 1.5 percent in 2009, halving organ damage. Yet he finds cooling and warming large organs presents a problem even if no ice is present.

Several leading researchers presented their work on better ways to freeze organs. These include directional freezing, and developing cooling and warming protocols that might put less stress on the organs.

John Bischof, a professor of mechanical engineering at University of Minnesota, has been using nanoparticles that absorb electromagnetic waves and re-emit them as heat to rapidly warm specimens. His goal is to warm large organs fast enough to prevent thermal stresses from accumulating. He has achieved heating rates of up to 200 C/minute.

Others have taken very different paths. Robert Ben, a professor of chemistry at University of Ottawa, has been designing cryoprotectants that control ice formation while minimizing cryoprotectant toxicity and thermal damage during heating and cooling. He has synthesized 1,600 unique analogs over the past five years, including at least one promising candidate.

Kenneth Storey, a professor of molecular physiology at Carleton University, believes researchers can preserve at room temperature by taking advantage of natural pathways in the same way that ground squirrels do in the winter. His work focuses on the use of microRNA to regulate mammal metabolism.

Others, such as Shaf Keshavjee of the Toronto Lung Transplant Institute, have developed ways to keep lungs alive for several days after harvesting them. This gives him time to repair and improve the function of the lung. His company, Perfusix, recently launched a portable device that enables physicians and medical researchers to do the same thing at their own locations.

While many challenges remain, the number of researchers in the field is growing rapidly, and so are the collaborations between disciplines as disparate as medicine, engineering, and chemistry.

“We have seen recent breakthroughs in ice blockers, cryoprotectants and vitrification,” said Sebastian Giwa, chair of the Organ Preservation Alliance and co-founder of two tissue preservation startups, Sylvatica Biotech and Ossium Health.

Read more about the Future of Organ Banking.