Emibet Ríos Roldán

Emibet Ríos Roldán

Emibet Ríos Roldán, a rising sophomore studying biomedical engineering at the Polytechnic University of Puerto Rico, researched how growth factors, mechanical stretch, and substrate stiffness influence in vitro activation of human cardiac fibroblasts to model patient-specific cardiac fibrosis seen in end-stage hypertrophic and dilated cardiomyopathy, aiming to improve disease models and antifibrotic therapies.

Hypertrophic and dilated cardiomyopathies (HCM and DCM) are major contributors to heart failure, a leading cause of death worldwide. A central driver of disease progression in these conditions is cardiac fibrosis, a process in which activated fibroblasts remodel the extracellular matrix (ECM), stiffen the tissue, and ultimately impair heart function. Recently, a distinct population of COL22A1-activated cardiac fibroblasts was identified in a subset of end-stage HCM and DCM patients. However, conventional fibroblast activation models fail to replicate this patient-specific phenotype in vitro.

Coming into the summer, I felt insecure about my skills and knowledge and couldn't imagine making meaningful contributions in such a space. But from the very first call with my incredible mentors, I felt certain it was going to be something special. And it was. I had the opportunity to work on fascinating research that pushed me to grow in ways I never anticipated. I advanced my technical abilities in the lab, refined my scientific communication, and learned how to navigate complex problems. I cherished saying my ‘good mornings’ to a remarkable group of peers in my cohort and lab, creating some of the most memorable moments of my life. My time in BSRP has left me with a renewed mindset that makes me feel prepared, confident, and motivated to keep pursuing my goals, discovering my passions, and shaping my future career.To develop more effective therapeutics for cardiac fibrosis, we must improve in vitro models of human disease. We aim to identify the most physiologically relevant combination of stimuli that replicates the COL22A1-activated fibroblast phenotype. We hypothesize that a combination of mechanical stretch, growth factors, and changes in plate stiffness can better recapitulate this phenotype. To evaluate this, we treated human donor cardiac fibroblasts with growth factors TGF-β1 and/or FGF2 across a range of concentrations, with or without mechanical stretch, and seeded them on plates of varying stiffness. We assessed cardiac fibroblast activation via immunofluorescence and qRT-PCR of markers COL1A1, ACTA2, and COL22A1 to quantify their expression and visualize cellular morphology. TGF-β1 upregulated COL1A1 and ACTA2, while FGF2 suppressed these but variably promoted COL22A1. TGF-β1 + FGF2 under 10% stretch and reduced plate stiffness reduced FGF2’s suppression, nearly restoring COL1A1 and ACTA2 to baseline and inducing COL22A1. This treatment partially induced a patient-specific activated cardiac fibroblast phenotype, advancing but not fully replicating the in vivo state. These findings support the development of late-stage HCM/DCM models and antifibrotic therapies.