Innovative Clinical Trial Could Transform Stem Cell Heart Regeneration Therapy

A multidisciplinary team at UHealth – University of Miami Health System and the University of Miami Miller School of Medicine is playing a key role in a collaborative clinical trial, funded by a $7 million grant from the U.S. Department of Defense, that could transform the use of stem cells to regenerate damaged heart tissues.

The team is co-led by Joshua M. Hare, M.D., the Louis Lemberg Professor of Medicine, founding director of the Interdisciplinary Stem Cell Institute and a heart failure/cardiac transplant cardiologist; and Aisha Khan, executive director of ISCI’s production laboratory.

“Cell therapy is emerging as a promising approach to helping patients with heart failure, a lethal, disabling and costly condition,” said Dr. Hare, who also serves as director of the Donald Soffer Endowed Program in Regenerative Medicine and senior associate dean for experimental and cellular therapeutics. “However, widespread adoption has been hindered by the invasive nature of delivering stem cells directly to the heart.”

Dr. Hare and Khan are the Miller School site principal investigators for the multicenter clinical trial to study a new approach to administering mesenchymal stem cells (MSCs) through an intravenous infusion rather than injecting them directly into the heart.

“If this approach is successful, cardiologists would be able to perform the infusions in an office setting, rather than an interventional cardiology lab,” said Dr. Hare. “That would make stem cell therapy accessible to far more patients in the U.S. and around the world.”

CATO Trial

As part of the study, MSCs will be produced from donor umbilical cord tissue in the ISCI’s GMP facility under the leadership of Aisha Khan, the principal investigator of cell manufacturing. This would include single or repeated intravenous administration of umbilical cord tissue derived mesenchymal stromal cells in ischemic cardiomyopathy (CATO) trial.

UHealth is recruiting 25 patients with ischemic cardiomyopathy, a weakening of the heart muscle that limits its pumping ability, for the phase IIA CATO trial, designed to study the safety and effectiveness of stem cell IV infusions. Another 25 patients will be enrolled at the University of Louisville, and 25 at the Texas Heart Institute, the other two study sites.

The ISCI’s GMP facility at the Miller School is a state-of-the-art facility designed to meet the highest standards of quality and safety in the production of stem cells for clinical use. The facility is equipped with the latest technology and equipment, and it is staffed by a team of highly trained and experienced professionals who are dedicated to ensuring the success of every project.

Khan recently spoke about the importance of quality control in the production of MSCs for clinical use.

“Quality control is absolutely critical in the production of MSC for clinical use. We have to ensure that every step of the process is carefully controlled and monitored to ensure that the cells are safe and effective for use in patients. This requires a lot of attention to detail and a commitment to excellence in everything we do.”

Studying Intravenous MSC Infusion

Dr. Hare believes the CATO trial is particularly important as heart failure cases continue to rise, reaching six million annually in the U.S.

“Current therapies have limited efficacy, and we need better strategies to address this major public health problem,” he said. “Our goal is to challenge the treatment paradigm that stem cells must be delivered directly to the heart. That approach requires invasive cell delivery methods and effectively limits treatment to one dose. In addition, large quantities of MSCs are needed, as these cells disappear rapidly after administration to the heart.”

Under the double-blind, randomized trial, one group of participants will receive four IV infusions of MSCs, a second group will receive one MSC and three placebo doses and a control group will receive a four placebo doses. Results of the trial will be based on improvements in left ventricular function as measured by cardiac magnetic resonance imaging (MRI) scans.

“We believe infusing MSCs intravenously will reduce inflammation of the heart and circulatory system,” said Dr. Hare. “We also want to see if repeated doses will have a better effect than a single dose.”

The CATO study will run in parallel to an ongoing clinical trial, also funded by the Department of Defense, on using stem cells to treat patients with non-ischemic cardiomyopathy, a different form of heart muscle disease.

“Our Miller School stem cell production, research and clinical teams are well positioned to study and treat both types of heart failure disorders,” said Dr. Hare, who has been at the forefront of stem cell research and therapy for more than a decade. “We look forward to continuing to advance the field of regenerative medicine.”

Tags: Aisha Khan, cardiomyopathy, Department of Defense, Dr. Joshua Hare, GMP facility, Interdisciplinary Stem Cell Institute, MSC infusion