Fibroblasts Slow Conduction Velocity in a Reconstituted Tissue Model of Fibrotic Cardiomyopathy

Teresa M. Spencer, Ryan F. Blumenstein, Kenneth M. Pryse, Sheng Lin Lee, David A. Glaubke, Brian E. Carlson, Elliot L. Elson, Guy M. Genin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Myocardial function deteriorates over the course of fibrotic cardiomyopathy, because of electrophysiological and mechanical effects of myofibroblasts that are not completely understood. Although a range of experimental model systems and associated theoretical treatments exist at the levels of isolated cardiomyocytes and planar cocultures of myofibroblasts and cardiomyocytes, interactions between these cell types at the tissue level are less clear. We studied these interactions through an engineered heart tissue (EHT) model of fibrotic myocardium and a mathematical model of the effects of cellular composition on EHT impulse conduction velocity. The EHT model allowed for modulation of cardiomyocyte and myofibroblast volume fractions, and observation of cell behavior in a three-dimensional environment that is more similar to native heart tissue than is planar cell culture. The cardiomyocyte and myofibroblast volume fractions determined the retardation of impulse conduction (spread of the action potential) in EHTs as measured by changes of the fluorescence of the Ca2+ probe, Fluo-2. Interpretation through our model showed retardation far in excess of predictions by homogenization theory, with conduction ceasing far below the fibroblast volume fraction associated with steric percolation. Results point to an important multiscale structural role of myofibroblasts in attenuating impulse conduction in fibrotic cardiomyopathy.

Original languageEnglish
Pages (from-to)3022-3028
Number of pages7
JournalACS Biomaterials Science and Engineering
Volume3
Issue number11
DOIs
StatePublished - Nov 13 2017

Keywords

  • Fluo-2
  • cardiomyocyte
  • conduction velocity
  • electrophysiology
  • engineered heart tissue
  • myofibroblast

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