A new stem cell therapy for heart failure is being tested in patients at the University of Louisville and UofL Health.

The trial is the first in the U.S. to test umbilical cord-derived stem cells in patients for heart failure and the first to use intravenous (IV) delivery of cell therapy for heart failure. It is the first trial in the world to test multiple doses of stem cell therapy for chronic heart failure.

Roberto Bolli, UofL professor of medicine, director of the UofL Institute of Molecular Cardiology and a UofL Health cardiologist, leads the study, which is enrolling patient participants at UofL, the University of Miami and the Texas Heart Institute. UofL Health is the only health system in Kentucky providing cell therapies for heart failure as part of clinical trials.

The Phase II clinical trial, dubbed the CATO trial, involves patients with ischemic cardiomyopathy, those who have had a heart attack resulting in scarring and heart failure. An $8 million grant to UofL from the Department of Defense is funding the four-year, multicenter trial, which aims to determine whether one or multiple doses of stem cells improve health and quality of life for heart failure patients.

If these cells are shown to be effective, the implications would be enormous. They would have significant potential to improve quality of life for heart failure patients and result in a paradigm shift in the treatment of heart failure.”

Roberto Bolli, UofL professor of medicine, director of the UofL Institute of Molecular Cardiology and a UofL Health cardiologist

The new therapy uses mesenchymal stem cells (UC-MSCs), which are produced from donated umbilical cords and are considered adult stem cells. The stem cells are isolated from the donated cords and expanded at the Interdisciplinary Stem Cell Institute cell production laboratory at the University of Miami. Each cord yields close to 4-5 billion MSCs, or 40-50 doses of 100 million cells each.

UC-MSCs are known to be anti-inflammatory and previously have been tested in ulcerative colitis, Crohn’s disease, COVID-19, graft vs. host disease and other conditions. This is the first trial in the U.S. in which the cells will be assessed for the treatment of heart disease.

Less invasive and more cost-effective delivery

The new cell therapy features several innovations which may reduce cost and barriers that limit access to stem cell therapy treatment for heart failure.

In this trial, the cells are administered through an IV line, a significantly more cost-effective and less invasive procedure compared to catheterization, which is necessary for delivering other stem cell therapies. An IV procedure can be done on an outpatient basis in a doctor’s office, IV clinic or hospital, making the therapy more accessible for those in underserved areas or who cannot go to a tertiary care center for treatment. IV delivery also makes multiple doses of the therapy feasible, which is not the case with catheterization.

“Off the shelf” cell availability

In addition, the cells can be manufactured and stored frozen, readily available for patients when they need them. This is a significant advantage over other cell therapies, for which cells must be manufactured from the patient’s own tissues, which increases cost and lead time for the treatment.

Heart disease is a major health problem throughout the world, including the United States where heart failure affects more than 6 million Americans and accounts for 1 in every 5 deaths, according to the CDC. Treatment options for individuals with heart failure currently are limited to medications, lifestyle modifications and in extreme cases, heart transplant or assist devices.

“Five-year survival for patients admitted to the hospital with heart failure is 50%,” Bolli said. “There are a lot of drugs available for the treatment of heart disease, but because of the abysmal prognosis, we need to improve treatment. If these cells prove to be effective, I hope they will become an additional treatment option for heart failure to reduce the morbidity and mortality for this disease.”

Along with Bolli, researchers for the trial include Joshua M. Hare, Louis Lemberg Professor of Medicine at the University of Miami Miller School of Medicine, Aisha Khan, executive director of the Interdisciplinary Stem Cell Institute cell production laboratory at the University of Miami, which will produce the cells from donor umbilical cord tissue, Emerson Perin, medical director of the Texas Heart Institute, and Joao Lima, director of cardiovascular imaging at Johns Hopkins Hospital, who will evaluate the MRI studies obtained from all participants.

Study details

Study investigators for the CATO trial, a randomized, double-blind, placebo-controlled clinical trial, plan to enroll 60 patients across the three centers: UofL, the University of Miami and Texas Heart Institute. Johns Hopkins will provide MRI evaluations of all trial participants.

Participants will receive four IV injections, approximately two months apart, in an outpatient clinic. Patients will be randomized to receive four cell treatments, one cell treatment and three placebo treatments or four placebo treatments.

Investigators will follow the patients for one year to evaluate their heart condition, exercise tolerance, quality of life, heart size and scarring via MRI and blood tests.