New UW solution stores organs even longer

In the late 1980s, University of Wisconsin–Madison researchers developed a synthetic solution that could safely store organs outside the body for longer than ever before. Their advance, known as the UW Solution, became the gold standard of organ preservation techniques.

Now, researchers at the School of Veterinary Medicine have raised the bar: By adding natural factors to the synthetic solution, they have further increased storage times and decreased organ damage. The finding could ease the nationwide shortage of transplantable organs and lead to more successful transplant surgeries.

UW–Madison veterinary surgeon Jonathan McAnulty, working with UW–Madison veterinary ophthalmologist Christopher Murphy and Texas Tech University professor Ted Reid, looked at the history of storage solutions and considered how their evolution to a purely synthetic solution may have affected stored kidneys.

Before the UW Solution, organs were kept alive with a blood-based solution that consisted of natural products. But because these solutions were natural, they could store livers for only six hours and kidneys for up to three days; they often resulted in organ damage, which could lead to chronic rejection or a recipient’s need for dialysis.

To improve these results, UW–Madison researchers Folkert Belzer and James Southard developed in 1986 a synthetic solution – the UW Solution – that increased storage times for organs such as livers and pancreases from six to 36 hours. More time led to more organs being transported between transplant centers, more rigorous tissue matches and, ultimately, more life-saving transplant surgeries.

Though the UW Solution could store organs longer than before, it still resulted in injury to the organs once storage times exceeded a day. “As we developed a totally synthetic solution,” McAnulty says, “we gained many benefits but also lost some benefits of blood-based solutions that were not recognized at the time.”

The benefits of the natural solutions, as the researchers found, included small proteins called trophic factors. These factors, which stimulate growth and DNA repair, had been investigated in other cell systems by Murphy and Reid for many years. When the researchers added a select group of trophic factors to the original UW Solution that stored canine kidneys, McAnulty says, “we had a marked improvement in the quality and length of storage.”

With the modified solution, which McAnulty describes as “totally synthetic but biologically active,” harvested kidneys could be kept alive for six days with little damage. “Dog kidneys stored for four days in the modified solution had damage equivalent to two days or less in the unmodified one,” he reports. The results are published in the August issue of the American Journal of Transplantation.

While it is unlikely that organs for transplant would ever be stored for up to six days, McAnulty says the study shows that the modified UW Solution slows the rate at which damage occurs to the harvested organ. “If injury accumulates at a slower rate,” he says, “then the damage that occurs at shorter time periods will be less.” By reducing that injury, McAnulty says he hopes the improved solution will favorably affect the donor pool and the number of successful transplant surgeries.

“The last major improvement of cold storage of kidneys was when the UW Solution was developed,” explains McAnulty. “Our research marks a quantum leap forward in the efficacy of kidney storage and provides newconcepts regarding the mechanisms active in preventing organ failure during storage.”

Currently, McAnulty and his colleagues are trying to identify other crucial trophic factors and understand how they work. A proposal to begin clinical trials is pending.