NIH-funded researchers extend liver preservation for transplantation

PUBLIC RELEASE DATE:

29-Jun-2014

Contact: Jessica Meade nibibpress@mail.nih.gov 301-496-3500 NIH/National Institute of Biomedical Imaging & Bioengineering

Researchers have developed a new supercooling technique to increase the amount of time human organs could remain viable outside the body. This study was conducted in rats, and if it succeeds in humans, it would enable a world-wide allocation of donor organs, saving more lives.

The research is supported by National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), both parts of the National Institutes of Health.

The first human whole organ transplant 60 years agoa living kidney transplantchanged the landscape of the medical world. Since then, transplants of skin, kidneys, hearts, lungs, corneas, and livers have become commonplace but due to a shortage of donor organs, more than 120,000 patients are still on waitlists for organ transplantation in the United States alone.

Current technology can preserve livers outside the body for a maximum of 24 hours using a combination of cold temperatures and a chemical solution developed by scientists at the University of Wisconsin-Madison in 1983. The solution helps keep the liver tissue from dying while in transit to the recipient site. This has helped increase the number of successful liver transplantsbut extending even further the time a liver can survive outside the body would provide many benefits. It would allow for more time to prepare the patient and ease logistics at the donor hospital site, reduce the urgency of rushing the organ to its destination, and expand the donation area to allow for transcontinental and intercontinental transplantationsthus increasing the chances of patients finding better matches while simultaneously significantly reducing costs.

The difficulty with long-term preservation of human organs stems mostly from the extensive tissue damage that occurs when organs are cryopreserved, frozen at temperatures of -320.8 degrees Fahrenheit. While successful for single cells and simple tissues, the problem is exacerbated with whole organs because of the multiple cell types and other structures that react differently to cold. To combat these problems, Martin Yarmush, M.D., Ph.D., and Korkut Uygun, Ph.D., investigators in the Center for Engineering in Medicine at Massachusetts General Hospital (MGH), Boston, have developed a four-step preservation technique that has tripled the amount of time that rat livers can be stored before transplantation.

In the June 29 online issue of Nature Medicine, the researchers describe their process. The first step is to employ the use of machine perfusiona way of delivering oxygen and nutrients to capillaries in biological tissues while outside the bodyto supercool the liver tissue without causing irreversible damage to the cells. In order to accomplish this, the MGH team added 3-OMG (3-O-methyl-D-glucose), a non-toxic, modified glucose compound, to the solution being delivered to the liver. The 3-OMG is taken up and because it cannot be metabolized by cells, accumulates in the hepatocytes (liver cells), acting as a protectant against the cold. The team also modified the solution by adding PEG-35kD (polyethylene glycol) to specifically protect cell membranes. Ethylene glycol is the active ingredient in anti-freeze, and it works by lowering the freezing point of a solution.

The livers were then slowly cooled below the freezing point, to 21 degrees Fahrenheit, without inducing freezingthereby supercooling the organ for preservation. After storing the organs for several days, the researchers again used machine perfusion to rewarm the organ, while also delivering oxygen and other nutrients to prepare the organ for transplantation.

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NIH-funded researchers extend liver preservation for transplantation