Research News

Cleveland Clinic was the first center in the United States to attempt uterus transplantation in 2016, and has recorded six live births from four patients since then. Though the program has been paused for a few years with plans to resume it soon, researchers have continuously studied methods to improve the procedure and benefit the health of uterus transplant recipients.

This includes researchers in the lab of Andrea Schlegel, MD, who is also a transplant surgeon. She and her team are testing the use of hypothermic oxygenated perfusion (HOPE) on human uteri – a preservation technique that prepares organs for transplantation.

Donated organs are typically preserved through cold storage – also known as the “icebox method.” The problem with this method is that the organ does not have anything flowing through its vessels. An organ that loses its blood supply also loses oxygen and nutrients, which results in tissue damage (also known as ischemic injury).

These problems are amplified for organs like the uterus, which is typically removed for donation after “life-saving” organs like the heart, liver and kidneys. That means the uterus could be without oxygen and nutrients for a significant amount of time (an average of 50 minutes, according to the Schlegel Lab’s study), sustaining greater ischemic injury.

The Schlegel Lab’s paper in the Journal of Clinical Medicine is the first report about this research and shows that HOPE is a beneficial technique for uterus preservation and assessment.

Why explore tissue perfusion?

HOPE, a recently developed method of preservation, uses a perfusion machine to keep an organ viable outside the body. The machine circulates cold, oxygen-rich fluid through the blood vessels, mimicking blood flow and extending the organ’s viability time.

The method has already been studied in liver, kidney and heart transplantation. The Food and Drug Administration recently approved it in the United States for liver transplantation. This had researchers in the Schlegel Lab wondering: Could HOPE be used for uterus transplantation?

Led by Keyue Sun, MD, a postdoctoral fellow in the Schlegel Lab, the team tested the viability of HOPE using six human uteri, which were provided for research purposes by Lifebanc. Their tests resulted in three important discoveries about the HOPE method:

• Similar to other organs, uteri were preserved better than with cold storage.
• The effects of ischemic injury were reversed.
• Researchers were able to measure specific biomarkers and potentially assess the condition of each uterus.

One specific biomarker, flavin mononucleotide (FMN), appeared to be an indicator of organ injury. The researchers were able to measure FMN levels in perfusion fluid – a test that could help scientists and surgeons assess the quality of a donated uterus before it is transplanted into a healthy patient.

“Donated uteri can sometimes experience a lot of ischemic injury, and seeing the positive effects of HOPE demonstrates the impact this preservation strategy can have,” Dr. Sun says. “We are very grateful for our partnership with Lifebanc. Their availability and support make the kind of research we envision possible, and that gives us confidence about the future of transplantation technology.”

Bolstering transplant across the globe

The Schlegel Lab’s innovative research directly influences the work of Cleveland Clinic’s Transplant Center, which operates across global locations. The goals of the Center are to standardize practices, share expertise and research across sites, and create a larger transplant research enterprise.

“Our clinically established concepts of transplantation, including HOPE, are practiced across all of our sites and we regularly share our experiences with caregivers in Florida and Abu Dhabi,” Dr. Schlegel says. “We can always improve and implement new methods, and our lab team believes that we can learn a lot from the uterus that is relevant for other organs – and vice versa. This research is exciting because of its potential for uterus transplant recipients, as well as how we ensure that organs are healthy for the transplantation procedure.”