After years of development by a team of Cleveland Clinic clinicians and engineers, a device that preserves human organs under physiologic conditions rather than on ice is undergoing a clinical trial at Cleveland Clinic and has been successfully used for liver transplants recipients in four cases to date. In each case, the liver began to function immediately after transplant and patients were discharged with normal liver function. The patients are doing well at this time.
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“We’re trying to recreate as closely as possible ex vivo the same conditions that exist in the body,” says Cristiano Quintini, MD, a liver transplant and hepatobiliary surgeon in the Digestive Disease and Surgery Institute (DDSI) and principal investigator of the clinical trial. “The results of the transplants so far using the normothermic machine have surpassed even our high expectations.”
Cleveland Clinic transplant specialists gained FDA approval in 2015 to conduct the single-center prospective cohort study. Up to 15 livers will be preserved by normothermic ex vivo machine perfusion for 4 to 18 hours and transplanted. Patients will be followed for 6 months, and outcomes will be compared to historical patients transplanted at Cleveland Clinic in the past five years using the traditional static cold preservation method.
Device offers multiple advantages
According to Dr. Quintini, the experimental ex vivo normothermic perfusion machine has several significant advantages over the standard method of static cold storage to preserve a transplant organ.
Maintaining a natural state. Traditionally, donor organs are cut off from their blood supply and placed on ice in a plastic cooler while being transported and awaiting implantation, leaving them vulnerable to damage from cold and lack of oxygenation. In contrast, the new device circulates oxygenated warm blood along with nutrients and medications to the donor organ, keeping it metabolically active while awaiting transplant.
Organs in cold storage must be transplanted quickly to help ensure their success: from four to six hours for the lung and heart, and within 24 hours for the liver and pancreas. Although this study stays within the time parameters of cold preservation for comparative purposes, Dr. Quintini believes that based on evidence from bench research and human studies from Europe, maintenance time could be further extended.
Ability to assess viability. An organ in cold storage is nonfunctioning, leaving no good way for transplant surgeons to assess its viability for transplant. Because surgeons are reluctant to implant an organ that may not succeed, organs in a questionable state are discarded. In contrast, because the normothermic device keeps organs functioning, their viability can be assessed by their ability to produce bile and by other laboratory indicators.
Organ can be made healthier. While being maintained on the normothermic device, an organ can be treated with medications and other interventions to improve its state.
Increasing organ supply
The device, which could be used for other organs in the future, could reduce the sizable gap between the supply and demand for transplant organs. Many of the thousands of people wait-listed for an organ die while waiting for one to become available. In 2014, around 2,000 livers were procured and discarded because of the limitations inherent to current cold preservation technology.
“Based on our experiments, we believe that about 60 to 70 percent of livers we currently discard could be transplanted successfully because of this technology,” says Dr. Quintini.
Homegrown Cleveland Clinic machine
A few other normothermic machines for transplantation are currently under investigation worldwide, but this study is the first to use a homegrown device. Cleveland Clinic Engineering Technician John Etterling was instrumental in developing the device and making it small, light and portable – key features for its successful use in the field. The machine went through extensive study over a period of four years before being used for the clinical trial.
Investigators at the Cleveland Clinic are exploring the new technology for preserving multiple organ types for transplant, including the kidney, intestines, pancreas, and even limbs.
The Cleveland Clinic Organ Recovery Center project is currently underway with plans to offer normothermic ex vivo perfusion for a variety of organs. The effort involves remodeling an operating room space in the main campus to house about eight stations with the new machines. Construction of the Organ Recovery Center will begin in December and is expected to be completed in three months. Widespread clinical use of this technology will depend on when various devices and proprietary solutions for perfusion receive FDA approval.
Dr. Quintini expects that these developments will make more viable organs available to Cleveland Clinic patients.
“Transplant medicine is undergoing a paradigm shift in how we preserve organs,” says Dr. Quintini. “And we will keep pushing the limits in the field.”