University of Minnesota achieves milestone in freezing organs before transplant

Scientists at the University of Minnesota have successfully transplanted rat kidneys that were thawed after up to 100 days in ultracold storage — a milestone that could one day revolutionize how and when human organs are transplanted.

The discovery, publicized by the U on Thursday, averts the formation of ice crystals that kills living tissue when frozen and the irreparable damage from uneven thawing.

John Bischof has been confronting those hurdles for years, and the mechanical engineering professor said he felt a sense of history-making when a frozen-then-thawed kidney resumed healthy function in a rat. Four more transplants produced the same results, with the kidneys functioning normally in 30 days, according to results published in Nature Communications, a peer-reviewed science journal.

"All of our research over more than a decade ... has shown that this process should work, then that it could work, but now we've shown that it actually does work," said Bischof, director of the U's Institute for Engineering in Medicine.

Effective cryopreservation has been a goal in many medical, biological and agricultural industries, but it offers Holy Grail potential for organ transplantation. Thousands of kidneys, hearts and livers are transplanted every year in a race-against-time system that procures organs right after donors die and rushes them while still viable to critically ill recipients.

Up to 20% of donor kidneys go to waste, often because they don't reach recipients in time.

One solution is to expand the supply. U researchers have studied transplants from animals to humans of pig islets or pancreases, and using human stem cells to grow biocompatible hearts or other organs.

Such alternatives remain experimental, increasing the need to optimize the existing supply. LifeSource, the local organ procurement agency, and Allina Health conducted a test flight of a drone carrying a pancreas to Mercy Hospital in Coon Rapids in 2021 to see if the technology could hasten delivery. Allina also participated in the trial of now-approved "heart-in-a-box" technology that keeps hearts beating in transit and maintains their viability.

Cryopreservation would remove the time pressure, reducing waste and allowing transplants to be scheduled when patients are healthiest and doctors are available — rather than at any time of day to beat the clock, said Dr. Erik Finger, a co-researcher and U transplant surgeon.

"Even if a fraction of [wasted donor organs] could be used, we could really start to chip away at the growing transplant waiting list," he said.

Freezing also would buy time to find the best match between donor organs and recipients, he said, and to address any racial or geographic inequities in organ distribution.

Improved freezing techniques have already changed in-vitro fertilization, reducing the pressure for infertility specialists to achieve pregnancies by transferring multiple, fresh embryos in patients. Freezing allows for genetic tests to select the best single embryos to transfer, maintaining high pregnancy rates without risks of multiple births.

Trouble is, the same techniques that safely freeze and thaw tiny embryos don't work as well when it comes to larger and more developed human organs. The outside of an organ can freeze and thaw faster than the center, which can cause irreparable damage.

Freezing damage can be prevented through vitrification, a rapid cooling process that suspends organs in a glassy, liquid state and prevents the formation of solid ice crystals.

The key is using enough antifreeze chemicals to protect the organs during cooling without being toxic, but thawing has been the next challenge, Finger said: "No one has been able to rewarm organs, in particular, out of that vitrified state."

The U discovery involves the infusion of tiny iron particles throughout an organ before it is cooled. The organ is later evenly thawed by being placed in a magnetic field that rapidly rotates it and heats up the iron particles. The particles and chemical preservatives are then washed out prior to transplant.

"You're sort of heating from within," Finger said.

U researchers have already built a magnetic coil capable of thawing human-sized organs, but Bischof said attempts at human transplants are years away. Nobody has even developed an equivalent cocktail of chemicals that could safely vitrify human organs, he said.

Next steps in the federally funded U research include repeating the success in a larger animal, such as a pig.