Bioengineering Lab Advances New Approaches to Congenital Heart Surgery

Jeffrey Jacot, PhD, who oversees the Jacot Lab for Pediatric Regenerative Medicine, is easily taken with his work.

All he has to do is open the door of his laboratory’s incubator. “There are cells or tissues in there beating on their own,” said Jacot, an associate professor of bioengineering. “It’s really awesome.”

Jacot conducts research at the University of Colorado Center for Bioengineering at the University of Colorado School of Medicine. His team specializes in engineering biomaterials that direct stem cells to build lab-grown 3D heart tissue.

This video shows a beating scaffold with cardiomyocytes in Jeffrey Jacot’s lab.

Severe heart defects in newborns come in a variety of forms, with hypoplastic left heart syndrome being one of the most common defects. The syndrome leaves the left ventricle, the chamber that pumps blood throughout the body, severely underdeveloped and nonfunctional. Thus, the right ventricle, the chamber that pumps blood to the lungs to be oxygenated, must take over.

The condition requires a series of surgeries “and doesn’t result in the same quality of life” for the child, Jacot said. “It usually causes a lot of other health issues later on, just because of different blood pressures, different flow rates. It is much more difficult to do a heart transplant because suddenly the patient receives a two-chambered heart and the lungs are not used to high pressure, so they fill with blood. So often a patient needs a heart and a lung transplant to overcome complications.

Modification of the core geometry

Jacot said the standard treatment involves fitting a patch, usually plastic, to redirect blood flow inside the heart. His team is taking a different approach: using bioengineering to stimulate the formation of new tissue in the heart, essentially altering the geometry of the organ for improved function.

Jeffrey Jacot explains how a heart valve simulator works in his laboratory in the Bioscience 2 building.

“We’re looking for ways to use a structure that has all the vasculature – capillary-like networks – to recruit heart cells, bringing in the body’s own cells and regenerating them,” he said. “You start with the capillary network, then it attaches to the host network, then the host network replaces it.”

In a recent study published in “Advanced Healthcare Materials”, Jacot’s team prevascularized a heart patch with human umbilical vein endothelial cells and amniotic fluid stem cells. In vitro, sitting in cultures inside the incubator, these 3D patches create tiny vascular networks and start beating on their own.

Study shows improved heart function

Jacot’s team then implanted two versions of the patches — the prevascularized 3D patches and the non-cell-loaded patches, which served as controls — into full-thickness defects in the cardiac wall of the right ventricle of rats. Two months after surgery, repair with the prevascularized patches resulted in improved heart function. The patched area showed greater vascularity and musculature, less fibrosis, and increased regenerative cellular infiltration compared to acellular control patches.

“It’s not a patch that covers an area of ​​the heart. It’s rather something

which provides therapy to the cells there – that’s something

which actually makes heart tissue. – Jeffrey Jacot, Ph.D.

The implant on the rat heart essentially became the wall of the right ventricle, in contact with the blood inside the heart. “It’s not a patch that covers an area of ​​the heart,” Jacot said. “Rather, it’s something that provides therapy to the cells there – it’s something that actually makes heart tissue.”

Although the results showed improvement, he said, heart function was still not comparable to a healthy native heart. “The current paper we submitted focuses on the in vitro study – going back to better ways to do prevascularization in vitro and looking at the communication between heart cells and other cells.”

In their work to grow heart tissue from cells found in amniotic fluid to repair congenital heart defects in newborns, Jacot’s team collaborates with cariologists and geneticists on campus as well as the dermatology research team of Ganna Bilousova, PhD, and Igor Kogut, PhD. In their work at the Gates Center for Regenerative Medicine, Bilousova and Kogut have developed a more efficient approach to reprogramming a patient’s diseased skin cells into stem cells.

Importance of collaboration

“They discovered how to generate stem cells from epithelial cells shed in urine,” Jacot said. “Then they make cells that can turn into any cell in the body. All of the cell types that we use are differentiated in our lab, so we collaborate a lot.

Jacot said his team is also working on a bioreactor project that involves conditioning heart tissue prior to implantation so that it is better prepared for incorporation into the heart. As the recent right ventricle study showed, “It’s not quite ready to be given directly to a patient or even a large animal, but it does show improved heart function. This shows us that our hypothesis is correct, and it gives us information to move on to the next iteration.

According to the bioengineer, congenital heart defects are an area that has long awaited improved treatments. “This research could make a truly transformative difference,” Jacot said. “We’ve been repairing hearts the same way since 1980. It would change the way we do congenital heart surgery.”

He added: “We deliver a lot of really important stuff that feeds into other areas of healthcare as well. I think the prevascularization strategy could be used for many advances in tissue engineering.