Dr. Celinda Kofron of Brown University

Cardiac fibroblasts (CFs) are known to regulate cardiomyocyte (CM) function in vivo and in two-dimensional in vitro cultures. Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-ECM interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. We examined the effect of CF activation on the regulation of CM electrical activity in a three-dimensional (3-D) microtissue environment and demonstrated that CF activation alone is capable of altering action potential and Ca2+ transient characteristics of CMs, leading to proarrhythmic electrical activity. We also used 3-D microtissues as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Our results also emphasize the importance of a 3-D environment where cell-cell interactions are prevalent, underscoring that CF activation and distribution in 3-D tissue plays a significant role in modulating CM electrophysiology and arrhythmias.

Biography:

Celinda Kofron, PhD is a biomedical engineer, earning her doctorate at Brown University with a focus on models of neurite guidance. As a postdoctoral fellow, she applied her knowledge of in vitro cues and cellular responses to cardiac models. Her recent work targets fibroblasts as key regulators of myocytes and contributors to heart failure and arrhythmias. Currently, she is the Associate Director of the Center for Biomedical Engineering and a Lecturer of Engineering at Brown University.