Transcatheter aortic valve replacement (TAVR) procedures have become a popular way of treating aortic valve stenosis, a condition in which the valve stiffens and worsens cardiac function. Following implantation of a prosthetic valve, the hearts of patients tend to undergo significant reconstruction around the treatment site, but the mechanics of this process are poorly understood.
It is difficult to study the hearts of living people, so a novel laboratory solution was necessary. Researchers at University of Colorado Boulder and University of Colorado Anschutz Medical Campus have come up with just the thing. They have developed biomaterial-based mimics of heart tissue that faithfully reproduce the environment of the heart. These mimics can be put through an implantation simulation and can then be studied in great detail.
Rat cardiac fibroblasts—which happen to be in the shape of a heart—grown on hydrogels mimicking cardiac tissue and treated with human serum. (Photo: Brian Aguado)
As aortic valve stenosis runs its course, fibroblast cells tend to convert into myofibroblasts, cells that lead to stiffening of tissues. Interestingly, following TAVR, myofibroblasts turn back into fibroblasts. Determining why this happens, why some people’s hearts experience a different amount of this change, and how to promote this process was the goal of the Colorado team. For example, men seem to exhibit more tissue remodeling following TAVR, so there’s already something different between men and women that can point to at least one aspect of the rebuilding process.
“Cardiac fibrosis due to excess deposition of extracellular matrix proteins is a massive problem,” said Timothy McKinsey, one of the study authors. “Among other things, fibrosis causes the heart to become stiff, impairing its ability to relax. We are excited about the potential of translating our current findings to develop innovative therapies for fibrotic diseases of the heart and vasculature.”
The team got hold of blood serum samples from aortic valve stenosis patients before and after they had valve implants installed. Using hydrogel biomaterials, they mimicked some of the important characteristics of cardiac tissue, including its stiffness. Cardiac cells were cultured within the hydrogel and then the protein expression within the blood serum was quantified. Using the technique, the researchers were able to spot which proteins were related to myofibroblasts turning into fibroblasts.
“Our lab is focused on engineering hydrogels as mimics of the extracellular tissue microenvironment,” said Dr. Kristi Anseth, distinguished professor of chemical and biological engineering and director of the Precision Biomaterials IRT. “The hydrogel system developed for these studies enables us to evaluate how patient-specific biochemical cues, found in human sera, can impact cellular phenotypes. Our patient-specific observations would not have been possible using conventional tissue culture plastic materials.”
Porcine valve fibroblasts grown on hydrogels mimicking valve tissue and treated with human serum. (Photo: Brian Aguado)
Study in Science Translational Medicine: Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation
Via: CU Boulder