Keeping the “Goldilocks” organ cool

Since the first human heart transplant nearly 50 years ago, the standard of care for transporting donor organs has changed little. A heart, kidney, or liver is harvested, cleaned, placed in a cooler on ice, and shipped off via ambulance or jet plane. There are fancier transport containers, but they can be prohibitively expensive or too unwieldy to travel long distances. For a particular organ—the intestine—a cooler simply won’t work. These intricate tubes demand more sophistication than a plastic bag on ice can offer. The intestine’s complex lining, or epithelium, “allows salts, fluids, and nutrients to go in and out on a regular but very regulated basis,” said John P. Geibel, D.Sc., M.D., vice chair and director of surgical research and professor of surgery (gastrointestinal) and of cellular and molecular physiology. “You don’t want to have secretory diarrhea, and you don’t want constipation. It’s the Goldilocks organ—[the environment] has to be just right.”

Besides the need for a delicately balanced environment, the intestine, teeming with bacteria, presents its own challenge. If the bacteria are not properly controlled, then parts of the intestine can fill with toxins and kill off healthy cells, putting the patient at further risk of infection. The problem with the standard ice transport method, said Geibel, is “that nobody is perfusing the tissue.” The intestine needs to be bathed in a constantly circulating liquid.

Geibel did not have to sit on his idea for long. In 2013, Joseph Zinter, Ph.D., associate research scientist and lecturer in the School of Engineering & Applied Science, invited Geibel to give a presentation to his students in a medical device design class. Geibel presented his idea for an Intestinal Preservation Unit (IPU), for which he had no prototype. A team of students signed up to “take the back-of-the-napkin drawing to a fully functional prototype,” Geibel said. While intestinal transplants are not as common as those of the heart, lung, or kidney, slight improvements in transplantation procedures could mean significant gains. Patients who cannot absorb nutrients due to a damaged or missing small intestine often face one option: getting nutrition through an IV or catheter.

When he met the engineering students, Geibel presented them with an extremely lightweight cooler and challenged them to fill in the missing pieces: a reliable battery and motor, a system of tubes to keep liquids moving throughout the intestine, and a temperature gauge and other tools for monitoring the status of the organ. It would be necessary to perfuse both the main blood supply, called the mesentery, and the lumen of the intestine. Within weeks, the engineering team presented a prototype, which contained a large battery and oversized top to fit the gauges and screens. “It was still kind of kludgy, but it was an engineering first, so we were very happy with it,” Geibel said. After the students graduated, Geibel kept momentum going by consulting with fellow transplant surgeons on the design. Soon, Geibel teamed up on another project with Jesse Rich and Jen Graze, students at the School of Management. In September 2014, the team established Revai, the company behind the medical device. By this time, Geibel and his team had tested swine organ explants in a “version 3.0” of the transport device, and all the animals looked healthy when examined in the histopathology lab after the transport.

To improve the design, Geibel and his team used a 3D printer to create a cooler top that could hold the batteries, tubing, and measuring devices, and would fit over the cooler. But the team stopped short of reinventing the wheel for a preservation solution. They used a commercially available hypothermic solution rather than trying to keep the liquids at body temperature. (The field is engaged in a fiery debate about whether hyperthermic, or body-temperature, transplants should be the standard of care rather than ice, Geibel said.) For sanitary and safety reasons, the interior of the IPU, as well as the tubing and connectors, are completely disposable. The Food and Drug Administration (FDA) requires this feature for all organ transport devices.

Transporting the intestinal organ can usually occur only within a narrow window of two to four hours. But the Revai team has kept an intestinal organ alive and functioning for eight hours, Geibel said. “We want to get our box so that it can keep things alive and keep things viable for longer periods of time,” he said.

So far, the group has reenacted an organ transplant in a veterinary operating room. Working with medical residents and fellows, Geibel and the Revai group watched while an animal intestine was harvested, placed in sterile towels, and taken to the “back table,” or what surgeons refer to as the organ transplant area. The intestine was then kept in the Revai cooler for eight hours. The team has also tested the transport of five donated human intestines. Without FDA approval yet, the transplants could not be used for implantation in a real-life patient. The next step, Geibel said, will be partnering with a high-traffic intestinal transplant center to conduct a clinical trial. “I think the number of transplants would go up dramatically if patients knew they had a device that gave them a very high [transplant] success rate,” Geibel said.