Lab moving beyond transplant research

Most people who drive by Port City Center on East Bay Street in Charleston have no idea what's happening inside, in the Organ Recovery Systems lab. Prestigious medical centers know, however, and so do leaders of federal agencies.

The 4-year-old research lab is expanding the boundaries of preservation in cells, then tissues and finally organs. Freezing temperatures of minus-135 degrees Celsius might store cells forever. Scientists here also develop chemical solutions and work with vitrification, which turns living tissue into glass and preserves it for later use.

"All I care about is that we can provide a patient with a transplant organ or tissue that he needs," said Kelvin G.M. Brockbank, senior vice president and chief science officer of the international Organ Recovery Systems.

Brockbank also heads the Charleston Research Center, which performs all the research for the corporation and analyzes results of clinical trials. "The organ shortage is getting worse all the time," he said. If organ banks could store what are now short-lived organs, they could be better matched to recipients and transported farther, which means fewer organs would be wasted, he pointed out. A doctor could order the right match when his patient needed it.

The center is developing ways to preserve kidneys, heart valves, blood vessels, cartilage, stem cells, products of tissue-engineering and pancreatic islets that can be transplanted to cure diabetes. In the process, discoveries have caught the attention of the military, oil companies, farmers, airlines, transplant surgeons and others.

The military envisions saving critically wounded soldiers in remote locations by replacing the patient's blood with a cooling solution that could slow metabolism to 10 percent of normal. That would reduce blood loss and brain damage while the soldier was evacuated to a well-equipped hospital.

Michael Taylor, vice president of research and development at the Charleston center, developed the solution, called Unisol, which also might be used to keep a patient on ice during neurosurgery lasting seven or eight hours.

Work done here in Charleston on cell and tissue preservation also has applications in protecting crops and in keeping sidewalks from freezing, David Kravitz, chief executive officer of Organ Recovery Systems, said from corporate headquarters in Chicago.

British Petroleum is interested in using products developed here to keep natural gas operations from freezing and approached the company about developing an industrial-strength antifreeze, Kravitz said. "You never know who is going to be on the other end of the phone," he said.

SCIENTISTS AND PATENTS

"Our facility in Charleston is unique in the world," said Kravitz, adding that the lab is the largest in the world focused on low-temperature medicine, or cryopreservation. Federal grants from agencies such as the Department of Commerce provide about 80 percent of the funding. The National Institutes of Health alone has paid for 60 percent of the applications the center has filed, Brockbank said.

The Charleston center recently landed more than $6.5 million in grants. "You can only do that if you're playing at the top of your game," Kravitz said.

Research partners or collaborators include Duke University, Harvard-owned Massachusetts General and Georgia Tech. "You are judged by the company you keep," said Kravitz, adding that those institutions are tops in cell preservation. The Medical University of South Carolina also collaborates with the center on several projects, including cartilage transplants for orthopedics, heart valves and blood vessels.

Brockbank remembers starting the center four years ago with just Kravitz in Seattle and himself in Charleston. Brockbank graduated from MUSC in 1980 with a Ph.D. in experimental pathology. About 16 scientists and other staff now work at the center, which has kept a low profile locally.

"We have been quietly doing our work," Brockbank said. "We anticipate that we will grow. We'll steadily grow."

The center is addressing what Brockbank describes as the major hurdle preventing donor organs from being fully used. More than 79,000 Americans and 150,000 people worldwide are awaiting organ transplants.

The research center first developed perfusion equipment and then an organ transporter for kidneys, with similar devices in the works for hearts and pancreases then --- ultimately --- larger livers. Organ Recovery Systems has 42 patents with 44 more pending in this country and abroad.

The company uses its own solution (which the Charleston center is refining) and perfusion equipment to improve the health of kidneys that otherwise would be rejected for transplant. Johns Hopkins and University of Maryland hospitals invited the company to open a Perfusion Service Center in Baltimore and apply what had been learned, Kravitz said.

So far, more than 40 percent of treated kidneys have been resuscitated and transplanted, with long-term survival matching that of ideal donor kidneys, he said. Company scientific advisor Louise M. Jacobbi reported that success at the International Congress of the Transplantation Society in Miami in late August.

CELLS, TISSUE, THEN ORGANS

Freezing organs and tissues would mean they could be stored much longer, but ice forms and damages cells. Organs deteriorate even more when transplanted. The research center is developing chemicals that prevent ice formation. The synthetic ice blockers also might be used on planes or crops in freezing weather, the same research that caught the eye of British Petroleum.

In vitrification, which turns tissue to glass, 55 percent of the water surrounding cells or an organ is replaced with chemicals before cooling. Ice never forms, so cells aren't damaged. The research center is developing chemical solutions that transform cells and tissues into a stable, solid glass state at minus-80 to minus-135 degrees Celsius.

Once tissues and ultimately organs are vitrified --- chemically stable and held almost like a fly trapped in amber --- they theoretically could be stored for hundreds of years at that low temperature, Brockbank said. "Our major interest is organs, but we have to start at the cell and tissue levels," he said.

The center is focusing on cartilage, which today lasts only a few days under refrigeration. With vitrification, the center has kept 80 percent to 85 percent of cartilage cells viable for transplant, whereas less than 12 percent remain viable after freezing, Brockbank said.

The National Institutes of Health just awarded the center an $880,000, two-year grant to expand its vitrification research into animal transplants and new methods that would use less chemical solution and warmer temperatures. MUSC will perform the vitrified cartilage transplants on large animals, Brockbank expects. Tests on humans would come next. Vitrified cartilage could help more than 100,000 patients with joints damaged by such things as sports injuries and arthritis.

Each year, hundreds of thousands of Americans could benefit from receiving transplants of tissue grafts or engineered tissue that is vitrified, Brockbank said. Within the next year, he anticipates working with whole organs, which the center already can vitrify but cannot bring back to life. Research also is under way on vitrifying heart valves, blood vessels and islets that would be transplanted into diabetics.

A Department of Commerce grant is taking the center into yet another area, drying cells and tissues to make them more stable and transportable. Rehydration would produce living tissue or cells. So far, the center has successfully dried some types of cells and kept them viable, Brockbank said. "We have a long way to go."