Cultivation in rotating bioreactors promotes maintenance of cardiac myocyte electrophysiology and molecular properties.

Published

Journal Article

We tested the hypothesis that cardiomyocytes maintained their phenotype better if cultured as three-dimensional tissue constructs than if cultured as confluent monolayers. Neonatal rat cardiomyocytes were cultured on biomaterial scaffolds in rotating bioreactors for 1 week, and resulting tissue constructs were compared with confluent monolayers and slices of native ventricular tissue with respect to proteins involved in cell metabolism (creatine kinase isoform MM), contractile function (sarcomeric myosin heavy chain), and intercellular communication (connexin 43), as well as action potential characteristics (e.g., membrane resting potential, maximum depolarization slope, and action potential duration), and macroscopic electrophysiological properties (maximum capture rate). The molecular and electrophysiological properties of cardiomyocytes cultured in tissue constructs, although inferior to those of native neonatal ventricles, were superior to those of the same cells cultured as monolayers. Construct levels of creatine kinase, myosin heavy chain, and connexin 43 were 40-60% as high as ventricle levels, whereas monolayer levels of the same proteins were only 11-20% as high. Construct action potential durations were 1.8-fold higher than those in ventricles, whereas monolayer action potential durations were 2.4-fold higher. Pharmacological studies using 4-aminopyridine showed that prolonged action potential duration and reduced maximum capture rate in tissue constructs as compared with native ventricles could be explained by decreased transient outward potassium current.

Full Text

Duke Authors

Cited Authors

  • Bursac, N; Papadaki, M; White, JA; Eisenberg, SR; Vunjak-Novakovic, G; Freed, LE

Published Date

  • December 2003

Published In

Volume / Issue

  • 9 / 6

Start / End Page

  • 1243 - 1253

PubMed ID

  • 14670112

Pubmed Central ID

  • 14670112

Electronic International Standard Serial Number (EISSN)

  • 1557-8690

International Standard Serial Number (ISSN)

  • 1076-3279

Digital Object Identifier (DOI)

  • 10.1089/10763270360728152

Language

  • eng