Fibroblasts support functional integration of purified embryonic stem cell-derived cardiomyocytes into avital myocardial tissue

Stem Cells Dev. 2011 May;20(5):821-30. doi: 10.1089/scd.2010.0398. Epub 2011 Jan 23.

Abstract

Transplantation of purified pluripotent stem cell-derived cardiomyocytes into damaged myocardium might become a therapy to improve contractile function after myocardial infarction. However, engraftment remains problematic. Aim of this study was to investigate whether murine embryonic fibroblasts (MEFs) support the functional integration of purified embryonic stem cell-derived cardiomyocytes (ES-CMs). Neonatal murine ventricular tissue slices were subjected to oxygen and glucose deprivation to simulate irreversible ischemia. Vital tissue slices served as control. Vital and avital tissue slices were cultured with or without MEFs before coculturing with clusters of puromycin-selected ES-CMs. Integration of ES-CM clusters was assessed morphologically, motility by long-term microscopy, and functional integration by isometric force measurements. We observed a good morphological integration into vital but a poor integration into avital slices. Adding MEFs improved morphological integration into irreversibly damaged slices and enabled purified ES-CMs to migrate and to confer force. We conclude that noncardiomyocytes like MEFs support morphological integration and force transmission of purified ES-CMs by enabling adhesion and migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Adhesion
  • Cell Differentiation
  • Cell Movement
  • Coculture Techniques / methods
  • Disease Models, Animal
  • Embryonic Stem Cells / cytology
  • Fibroblasts / cytology*
  • Heart Ventricles / pathology*
  • Mice
  • Microtomy
  • Myocardial Infarction / pathology
  • Myocardial Ischemia / pathology*
  • Myocytes, Cardiac / cytology*
  • Pluripotent Stem Cells / cytology*
  • Regenerative Medicine
  • Tissue Engineering / methods*