Research News

Just like the organs in our living bodies, the viability of harvested organs depends on one key resource: oxygen. Despite the transplant team’s best efforts to protect their precious cargo on a limited timeline, lack of oxygen can result in injury and tissue deterioration to the organ, making it unsuitable for transplant, a result that is devastating to recipients, donors and their loved ones.  

New knowledge of how these organs work, both when harvested from donors and after being transplanted to patients, allows Cleveland Clinic to develop innovative ways improve patient outcomes.

Along with improving transplant techniques, research identifies markers in the immune system that allow doctors to predict a successful transplant – and when to keep an eye out for problems.

“Cleveland Clinic has one of the highest-volume, most robust transplant centers in the world,” says Robert Fairchild, PhD, Inflammation & Immunity, who leads the transplant immunology research program at the Lerner Research Institute. “The number of organ transplant tissue samples available to our investigations, combined with the strength of our basic science group and opportunities for clinician collaborations, has allowed us to conduct investigations that have helped improve success rates of organ transplantation procedures both nationally and globally.”

Only one-third of U.S. patients waiting for an organ in 2021 received the life-changing surgery, according to federal numbers. The main reason for this gap is a lack of donors, which makes it even more important to preserve the quality of available organs once doctors find a match.

Dr. Fairchild is collaborating with Cleveland Clinic's Transplant Center to increase the number of organs available and increase the success of the transplant procedures. The research effort is part of a system-wide initiative at Cleveland Clinic to increase successful organ transplants. Transplant numbers overall went up 18% year-over-year from 2020 to 2021.

Revitalizing unsuitable organs

Dr. Fairchild and his team have made a number of seminal discoveries in the field of transplantation and immunology. Working alongside clinicians, their translational science focuses on heart and kidney rejection, in addition to working with liver, kidney and lung transplant teams.

“Healthy organs can become too damaged to transplant if they run out of oxygen on the way to the patient,” Dr. Fairchild says. “We want to ensure the best for our patients and the donors’ families. So we are asking how we can make more organs viable for these procedures.”

The organ can stop working properly because of cold injury from sitting on ice, or it can run out of oxygen, rendering it unusable. Dr. Fairchild and clinical collaborators including Koji Hashimoto, MD, PhD, Kenneth McCurry, MD, and Cristiano Quintini, MD, are part of a national collaborative studying a new practice, ex vivo organ perfusion, which aims to prevent or even reverse the damage that can render donated organs unsuitable.

Traditionally, organs are kept on ice during transport. The cold temperatures stabilize donated organs, but can lead to injury. Ex vivo organ perfusion actively supports donated organs by treating them through ventilation and blood flow. This method can help recondition lower quality organs and eliminates the need for cold storage. While just 1% of Cleveland lung liver transplants were involved this new practice in 2016, that number increased to 25% in 2020.

Reducing the risk of rejection

Transplant recipients face a risk of “graft rejection,” which causes a person’s own immune system to turn against their new organs.

When the body detects a foreign organ, it activates the immune system, prompting T-cells and antibodies to attack the new organ. These attacks, called immune-mediated inflammatory responses, cause inflammation and tissue injury in the transplanted organ. They often lead to organ injury and ultimately can cause the body to reject the organ entirely.

When measured in a patient’s body, molecules associated with this immune response can predict the likelihood that any individual patient will reject their new organ. These molecules, called biomarkers, allow caregivers to personalize the pre- and post-surgery treatment plans and help physicians monitor the graft to avoid the rejection response altogether. The research program has already yielded promising results. New data from the Fairchild Lab suggests that physicians can track elevated levels of mitochondrial DNA in patient blood to improve patient care.

This is not the first biomarker discovery the research team has made. In 2015, Dr. Fairchild collaborated with Roslyn Mannon, MD, Professor of Medicine and Microbiology and Immunology at the University of Nebraska Medical Center, to identify biomarkers in kidney transplant patient urine that can identify patients at risk of transplant failure before the symptoms emerge.  Drs. Fairchild and Mannon developed a non-invasive test that allows investigators to use gene expression data and accurately diagnose rejection with almost five times the accuracy of similar assays.

“We believe this technology will help decrease the dosing of immunosuppressant drugs that patients take after a transplant and greatly improve the patient’s quality of life,” Dr. Fairchild says.