by George Taniwaki

A new organ preservation method may help increase the number of transplants. It could dramatically increase the survival of patients with end stage liver or heart disease.

Background

The most common organ to be transplanted are kidneys. Part of the reason is that there are lots of patients with kidney failure waiting for a transplant. And part of the reason for that is patients with kidney failure can be placed on dialysis therapy while waiting for a donor organ. This allows them to survive several years while waiting for a donor organ. Patients requiring a replacement for failed hearts, lungs, and livers cannot wait. They must be transplanted quickly. If an organ is not available, they will die.

The other reason kidneys are the most common organ to be transplanted is that donor kidneys can be kept in ice water storage for 24 to 36 hours prior to transplant and still remain viable. This provides time to run crossmatch tests using blood samples from the donor and several possible recipients, contact the best matching patients and their surgeons, get them to the hospital, and transport the donor organ to the hospital. Hearts can only be stored about 4 hours and livers can only be stored about 12 hours. This often is not enough time to prepare for surgery and so the donor organ has to be discarded, unused.

I discuss some of these issues in earlier blog posts. For instance, see my Nov 2010 blog entry and May 2010 blog entry.

New and supercool protocol

In a paper published in Nature Medicine, Jun 2014 (subscription required), Tim Berendsen at University Medical Center in Utrecht, the Netherlands, Bote Bruinsma at Massachusetts General Hospital and Harvard Medical School, and others have developed a new protocol to supercool organs below zero (32 deg F) without freezing them. Their technique was tested on rat livers, but would likely work on human livers and would work with other organs, including kidneys. A good explanation of the process is included in a Jun 2014 press release.

HarvardRatLiver

Figure 1. Supercooled rat liver being perfused with new solution developed by Harvard researchers. Photo from Harvard University

Their technique involves four steps. First, the organ is placed in a vessel while an ice cold solution (usu. about 4 deg C, 39 deg F) is circulated through it, a process called perfusion. The solution contains dissolved oxygen and nutrients such as glucose that help keep the organ alive. This is already the standard procedure for perfusing organs.

What is new, is the perfusion solution and the next steps. The perfusion solution contains PEG-35kD (polyethylene glycol) and other proprietary ingredients (to be commercialized) that act as an antifreeze. This allows the solution and the liver to be carefully cooled to -6 deg C (21 deg F) in a way that avoids the formation of ice crystals that could damage the cells in the liver. The liver can remain perfused in the supercooled condition for up three days and remain viable. Then the liver is carefully warmed to above freezing and prepared for surgery as normal.

HarvardRatLiverChart

Figure 2. Chart showing temperature profile of liver using proprietary perfusion solution and supercooling protocol. Image from Nature Medicine

Extending the viable time for liver transplant from 12 hours to three days would be a huge change. It would allow many more transplants to occur, with a corresponding decrease in the number of patient deaths caused by a shortage of organs. Just as important, by allowing time for multiple crossmatch tests to be conducted, it could potentially improve the matching of organs to patients.

The next steps in the research is to try livers from larger animals and to test the protocol on other organs.

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