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Novel Research on Calcific Aortic Valve Disease: UPMC’s Collaborative Approach to Translational Science

May 28, 2021

Researchers at the St. Hilaire laboratory at the University of Pittsburgh School of Medicine have been studying why healthy cells in the aortic valve transdifferentiate to calcified ones. To conduct this novel research, Cynthia St. Hilaire, PhD, assistant professor of medicine, Division of Cardiology, and her team developed a protocol for collecting valve samples and isolating valve cells in a recent paper, “Isolation of Human Primary Valve Cells for In vitro Disease Modeling.”

Through utilizing a cold storage solution that experts in the UPMC Advanced Heart Failure Center use for heart transplants, Dr. St. Hilaire’s study demonstrates that isolated aortic valve cells can survive and retain their phenotype several days after being removed from the donor. 

“We were able to capitalize on that knowledge and use it for our tissue procurement to keep our cells viable and living for longer, such that we can get larger yields,” said Dr. St. Hilaire. 

This novel research, which Dr. St. Hilaire received over $2 million in funding for over the course of five years, was made possible because of collaboration between the UPMC Heart and Vascular Institute (HVI) and the St. Hilaire laboratory at the University of Pittsburgh. Dr. St. Hilaire noted that collecting human tissue cells for this research involves teamwork between her lab and clinical leadership within the HVI Center for Thoracic Aortic Disease, led by co-director Ibrahim Sultan, MD.

“This collaboration is something you want,” said Dr. St. Hilaire. “It is something that differentiates the Heart and Vascular Institute, because it is hard to do. It’s not just at the level of a patient wanting to participate in the study; it’s not just at the level of having all the proper IRBs in place. There is a large amount of people on the side of the surgeon that have to help make this research happen.”

During the study, Dr. St. Hilaire’s team found that the use of a cold storage solution when transporting valve cells from surgical site to the lab stabilized them. Thanks to the new protocol, the cells can remain viable after 48 hours post excision. 

The ability to collect large amounts of valve specimens – Dr. St. Hilaire currently has a biobank of more than 250 valve specimens – is the first step of understanding the mechanisms that govern how healthy valve cells undergo calcification. Thanks in large part to the bridge between the clinical and research arms, Dr. St. Hilaire has been able to conduct additional research on the role telomerase plays in valve calcification, which researchers believe is required for the osteogenic phenotypic switching of a healthy cell to a calcified one.  

The overarching goal of this research is to learn the many steps cells take in the calcification process and why. Once researchers understand these steps, non-surgical treatments for aortic stenosis can be developed, which is the future of cardiac care at UPMC and beyond.  

“If we are able to identify a druggable target that is specific to this transition, we could potentially develop therapeutics against that,” said Dr. St. Hilaire. “You can’t create novel therapies unless you identify all the different steps to potentially target.”

About UPMC Heart and Vascular Institute

The UPMC Heart and Vascular Institute has long been a leader in cardiovascular care, with a rich history in clinical research and innovation. As one of the first heart transplant centers in the country and as the developer of one of the first heart-assist devices, UPMC has contributed to advancing the field of cardiovascular medicine.