Summer 2017

Heart-warming discovery

A new method of warming tissue may one day make more organs available for transplant


Despite advances in organ transplant technology, doctors still cart around donor organs much as they have for the last half-century—suspended in 39°F saline and packed in an ice-filled plastic cooler.

Once an organ is removed, it’s a race against time to get it to transplant, as the icy conditions can damage the tissue in a matter of hours (as few as four in the case of a human heart). 

But now, a research team led by John Bischof, Distinguished McKnight University Professor and holder of the Carl and Janet Kuhrmeyer Chair in Mechanical Engineering, has found a way to successfully rewarm animal heart valves and blood vessels that have been preserved at temperatures of -140°C. 

The team’s work is a major step toward preserving tissue for much longer periods and even establishing tissue and organ banks.

“If you don’t have a time issue, you can do far better matching,” Bischof says. “You can really optimize how organs are used, and you won’t waste a good organ.”

Double jeopardy

For decades, researchers have sought to preserve organs through vitrification—supercooling them to a glasslike condition without the formation of ice crystals that destroy tissue. Once vitrified, organs could be stored indefinitely without damage. 

Scientists solved the problem of ice-crystal formation partly by infusing tissue with a complex chemical cryoprotectant—basically antifreeze—while cooling it. The more vexing problem has been preventing ice from forming as the sample warms. 

“Basically it’s double jeopardy,” Bischof says. “You’ve got the crystallization that might occur on the way down, and you’ve got the crystallization that will surely occur on the way up. You need to outrun it.”

“If you don’t have a time issue ... you can really  optimize how organs are used.”
John Bischof, professor of mechanical and biomedical engineering

That means heating vitrified tissues quickly, up to 55°C per minute. But unless the tissue is tiny—think embryos and scraps of blood vessels smaller than a milliliter (about a fifth of a teaspoon)—the sample warms unevenly and ice forms in the cold spots. 

Bischof surmounted the problem by marinating the tissue in a solution of both cryoprotectants and iron oxide nanoparticles. Each nanoparticle is about 14 nanometers across and coated with silica, which helps ensure that they diffuse evenly throughout the sample. He then radiated the tissue with high-energy radio frequency fields, which pass through harmlessly but energize the nanoparticles, turning them into microscopic heaters. The tiny heaters warm the tissue evenly—and quickly enough that ice crystals can’t form. 

Bischof successfully warmed vitrified pig arteries and aortic heart valve leaflet tissues weighing nearly 2 ounces without damage. Subsequent imaging showed that flushing with the cryoprotectant removed all the iron oxide particles. And testing showed no significant biomechanical changes in blood vessel length or elasticity.

“The nice thing about the technology is that it’s scalable. We can envision going up to a liter or even larger,” Bischof says. That would put human organs, such as kidneys and even hearts, within the realm of possibility.

A connected U

Bischof—also associate director of the Institute for Engineering in Medicine and a member of the Masonic Cancer Center, University of Minnesota—has been working on nanoparticle heating for about 10 years, first to heat and destroy cancer cells. But as he learned about the interest in cryogenic preservation of tissue, he began experimenting with using nanoparticles in thawing. “From there,” he says, “it ballooned very quickly.”

Important contributions came from Christy Haynes, Elmore H. Northey Professor and vice chair of the College of Science and Engineering’s Department of Chemistry, who developed the biocompatible silica coating that prevents the nanoparticles from clumping. Michael Garwood, a professor in the Medical School’s Department of Radiology, developed the imaging technology that determines whether the iron oxide nanoparticles are evenly distributed throughout the tissue sample. 

“If the nanoparticle is properly coated, then the amount of iron we image can tell us how well it’s going to heat,” Bischof says. 

He says his position as the Kuhrmeyer Chair “definitely helped me over several humps between proposals to keep students paid, materials and supplies coming in, and allowing travel to several important meetings.”

Bischof hopes to continue research on rodent vessels and hearts with University of Minnesota Health transplant surgeon and assistant professor of surgery Erik Finger. 

The hope is to one day be able to transform the field of organ transplantation. Says Finger, “Successful cryopreservation—or banking—of human organs and tissues could revolutionize the way organs are recovered, stored, and allocated for transplant, increasing the number of organs available and saving lives in the process.”

Greg Breining is a Twin Cities writer.