One out of 1,000 infants is born with just one functional heart ventricle instead of two, making it hard for oxygenated blood to pump effectively throughout their bodies. Today, babies with this condition (single-ventricle congenital heart defects, or SVCHDs) typically undergo a heart surgery called a Fontan operation, where a synthetic or tissue-engineered tube is used to bypass the defective pump and connect oxygenated blood directly to the pulmonary artery. Without surgery, there is a 70% mortality rate associated with SVCHDs.
While the Fontan surgery is often lifesaving, it is not a perfect fix. The plastic tube, for one, does not grow with the baby, requiring infants and children to undergo several surgeries throughout their lives. The plastic tube is also prone to infection and clotting and, unlike functional ventricles, cannot pump.
In response, the National Institutes of Health (NIH) recently awarded Yibing Qyang, PhD, associate professor of medicine (cardiovascular medicine, pathology) and associate professor of biomedical engineering, and his colleagues in his laboratory a $2+ million R01 grant to support research to create an artificial blood vessel that can grow, pump, and resist infection and clotting.
“Our first aim is to solve the immediate clinical problem, which is to create a tube that is not prone to infection, clotting, or stenosis and does not require multiple surgeries. We hope to have a solution to this clinical problem in five to 10 years,” said Qyang. “But we are also interested in a second-generation product that could provide a pumping activity to generate another working ventricle for the patient.”
Specifically, the R01 grant will support the team’s use of pluripotent stem cells and tissue engineering to generate immunocompatible, universal tissue-engineered vascular conduits. This research aims to establish a foundation for readily available, mechanically active “tubes” to provide a curative treatment for patients born with SVCHDs.
“We’re proud of Yibing and his team for their ingenuity and dedication to this research, which has the potential to transform the way we deliver care to patients with SVCHDs,” said Eric Velazquez, MD, Robert W. Berliner Professor of Medicine and chief of Yale Cardiovascular Medicine. “This work underlines Yale’s unique ability to connect the best and brightest from different fields to work together to solve some of the toughest clinical challenges.”
The project brings together stem cell biologists, vascular immunologists, and physician-scientists who treat single-ventricle defects and has the potential to change the paradigm of clinical care for SVCHD. This collaboration of different specialties is integral to expediting the clinical application for this strategy, says Qyang. “I'm a PhD scientist who loves engineering stem cells. But working alone, this would not be a clinically feasible paradigm. We need a village of people interested in treating this disease.”
Qyang, who trained in biochemistry and microbiology before getting his PhD in molecular genetics, was drawn to the field of cardiovascular research because it provided an opportunity to combine basic research with patient care. Now, he sees this same excitement in his physician-scientists, graduates, and post-docs, who have direct exposure to the operating room and can see firsthand how their research improves therapy options available to patients.
Qyang and his team continue to look at other applications of this technology. They already hold a patent for synthetic blood vessels that can repair the heart and vessels to treat patients with end-stage cardiovascular failure, and they are looking for opportunities to collaborate with clinicians and investigators across the field of medicine to identify other clinical problems their research may be able to address.
“I would love to see this impact patient care – and not 50 or 100 years from now,” Qyang said. “I want to see its impact in my lifetime.”
Other members of the research team include Stuart Campbell, PhD; Jordan Pober, MD, PhD; Robert Elder, MD; Peter J. Gruber, MD, PhD; George Tellides, MD, PhD; Hangqi Luo, MD, PhD; Jinkyu Park, PhD; Muhammad Riaz, PhD, MPhil; Yingxin Lin, PhD; and Lingfeng Qin, MD, PhD.
The latest NIH grant is just the latest in a string of R01 grants from the NIH for this program. This research has also received funding from the U.S. Department of Defense, the Connecticut Regenerative Medicine Research Program, and the Yale Stem Cell Center Chen Innovation Award, demonstrating the promise and potential impact of this work.