Pressure control, the key to liver preservation

Seventeen people die each day waiting for an organ transplant in the United States. Only 10% of the worldwide need for organ transplantation is estimated to be met. It has been suggested that the ability to replace organs on demand could impact health care on par with curing cancer. Developing efficient ways to preserve organs is essential to help bridge the gap.

Yoed Rabin has been studying cryopreservation and developing enabling technologies for three decades. His latest project, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health), will seek to preserve the liver, one of the most complex and in-demand organs, in cryogenic temperatures.

“If ice crystals form in an organ during preservation, cells are destroyed,” explained Rabin, a professor of mechanical engineering. “One way to create more favorable conditions for cryopreservation is to elevate the pressure surrounding the organ.”

A promising method to elevate the pressure relies on constraining the natural tendency of water to expand upon freezing when placed in an extremely rigid container, and the application is known as isochoric cryopreservation. Unfortunately, the hazardous effects of crystallization must take place somewhere in the container for isochoric cryopreservation to work. Rabin is aiming at advancing this approach to the next level by eliminating the need, and even the possibility, for ice to form in the cryopreservation container.

I sense that we are only five to 10 years away from seeing this method in clinical practice.

Yoed Rabin, Professor, Mechanical Engineering

“I’ve devoted my research career to developing tools and enabling technologies that I believe will bear fruits in my lifetime,” said Rabin. “I sense that we are only five to 10 years away from seeing this method in clinical practice.”

The $1.3 million dollar grant builds on Rabin’s legacy in the field.

“My research continues to be an extension of itself,” he said. “Oftentimes projects don’t start and end in isolation from the broader effort, and I am thankful that my work sees a consistent line of progress over such an extended period of time.”

The project is conducted in collaboration with Charles Lee at the University of North Carolina Charlotte, a well-established leader in the field, with decades of experience in liver research. Lee will test the new cryopreservation technology on animal models. The advisory panel to this project includes transplant surgeons and experts in the field from Harvard Medical College, Mayo Clinic, and the University of Minnesota.

Extending liver preservation time beyond the current 16 to 24 hours will greatly solve many of the logistical issues of donor livers. This will allow greater usage of donor livers because a broader base of recipients located at greater distance away from the donor will become possible. The team’s isolated liver perfusion and transplant models should quickly assess proof of concept and feasibility of this new technology.

Rabin collaborates with advisors and colleagues scattered across the United States including transplant surgeons, physiology experts, cryobiologists, and his own former students who now work in industry. He is a senior member of the Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio), an NSF center that aims to “stop biological time” and extend the ability to bank and transport cells, tissue, organs, and more.

“The idea behind working in such a supportive and diverse environment is that we can accelerate progress by working as closely as possible to the end user, which in this case is clinical use.”