University of Pittsburgh graduate student Madeline Cramer received an F31 award from the National Institutes of Health for her regenerative medicine research that may help improve outcomes in cardiac disease. Ms. Cramer studies bioengineering in the Swanson School of Engineering and works in the lab of McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor of surgery at Pitt.
Dr. Badylak’s lab focuses on the use of biologic scaffolds composed of extracellular matrix (ECM) to facilitate functional tissue and organ reconstruction. Present within all tissues and organs, ECM provides essential structural support and also initiates biochemical and biomechanical cues. Ms. Cramer’s project will look at myocardial infarction (MI) and examine how a specific protein embedded within the ECM may affect the underlying mechanisms behind the scaffold’s therapeutic response.
“Following myocardial infarction, cardiomyocyte death initiates an intense inflammatory response which is necessary to clear the debris of the dead cells,” explained Ms. Cramer. “However, a prolonged pro-inflammatory state is associated with immune-driven fibrosis that can progress to heart failure.”
Heart failure is a costly condition that affects millions of adults in the United States. Tissue engineered biologic scaffolds derived from ECM have been shown to promote an anti-inflammatory phenotype in macrophages and reduce fibrosis after MI in pre-clinical and clinical studies, but the underlying mechanisms driving this response are only partially understood.
“Previous work in the Badylak lab showed that ECM is an abundant source of extra-nuclear interleukin-33 (IL-33), a protein that is stored and protected from degradation within matrix-bound nanovesicles (MBV),” said Ms. Cramer. “My research aims to delineate the roles of MBV-associated IL-33 in mediating the pro-remodeling effects of ECM through in vitro and in vivo models of myocardial infarction.”
Demonstrating that IL-33 containing MBV can dampen the fibrotic response following MI may prove to be a significant advancement in the treatment of MI and the prevention of subsequent heart failure.
“Maddie has worked extremely hard and is very deserving of this award,” said Dr. Badylak. “I’m confident that the results of her work will have a significant impact upon the field.”
Illustration: University of Pittsburgh.