BME Seminar Series: Corin Williams, Ph.D.
Tuesday, March 3, 2015
Goergen Hall 101 (Sloan Auditorium)
"Cardiac Extracellular Matrix as a "Regenerative" Biomaterial for the Young Heart"
Corin Williams, Ph.D.
Department of Biomedical Engineering
Abstract: Children born with congenital heart defects (CHDs) or disorders often develop heart failure at a young age. For these patients, heart transplantation is the only successful long-term option. Unfortunately, pediatric donor organs are scarce and waiting list mortality is high. Thus, there is a great need to develop novel strategies to repair or regenerate the defective young heart. The extracellular matrix (ECM) plays an important role in guiding cell behaviors including proliferation, differentiation, and maturation. In this talk, I will present three related projects which explore cardiac ECM as a “regenerative” biomaterial. The first project explored the effect of developmental age of the cardiac ECM on the proliferation of neonatal rat cardiomyocytes. I found that fetal cardiac ECM significantly promoted cardiomyocyte proliferation compared to neonatal and adult ECM and control substrates. Further, the complex ECM was better than single ECM proteins. However, the translational potential of fetal ECM is limited due to ethical concerns and low yields of material. Therefore, I next developed partial digestion of adult cardiac ECM (PD-ECM) as a method to extract proliferative cues. I found that “short” PD-ECM significantly promoted cardiomyocyte proliferation similar to fetal ECM, while “long” PD-ECM which was fully digested promoted cardiomyocyte maturation. Interestingly, the composition of fetal ECM and short PD-ECM was different, suggesting different mechanisms; we are currently exploring specific peptides responsible for the proliferative response. Finally, I will describe my work with isolating and characterizing c-kit+ cardiovascular progenitor cells (CPCs) from pediatric patients with CHDs. I developed cardiac ECM-fibrin hybrid scaffolds with tunable composition and stiffness and found that CPC vascular differentiation was affected by changing these properties. Furthermore, the ECM hybrid scaffolds are injectable, demonstrating their potential for minimally invasive therapies. All together, this research is laying the foundation for ECM-based approaches to treating CHD patients in the future.