Enhanced cardiac differentiation of mouse embryonic stem cells by electrical stimulation

Paul R. Bidez, J. Yasha Kresh, Yen Wei, Peter I. Lelkes

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

8 Scopus citations

Abstract

Cardiovascular diseases account for more deaths than any other illness. Cardiac tissue engineering has turned to embryonic stem cells as a renewable source of myocytes for use in tissue replacement. Existing methods for stem cell differentiation toward the cardiac lineage are relatively non-specific, yielding low numbers of myocytes with varying contraction frequencies and strengths. Here we describe novel experimental approaches, utilizing an electrical stimulation regimen, aimed at increasing the efficiency of cardiac differentiation from mouse embryonic stem (mES) cells. These methods generate cardiac myocytes with functional characteristics that more closely resemble native tissues. The amplitude, duration, and frequency of the electrical stimulus as well as the timing of its onset are some of the critical experimental parameters that determine the enhancement of cardiac differentiation. In order to form embryoid bodies, an optimum differentiation regime was followed incorporating the hanging drop method followed by suspension culture and subsequent post-plating on conductive slides with electrical stimulation. Approximately three times more stimulated mES cells exhibited evidence of cardiac differentiation than their non-stimulated counterparts, as determined by the expression of ventricular marker myosin light chain-2v. Spontaneous contractions of the stimulated cell populations began up to 1 day earlier and had an average beat frequency close to that of the stimulus applied during differentiation. The spontaneously contracting regions had larger areas of contraction, which beat more rhythmically, as determined by real-time digital imaging analysis. Our results suggest that appropriate electrical stimulation generates greater numbers of more robust cardiac myocytes, which in turn may be better suited for repairing or regenerating an ailing heart and for use as 3D model systems for drug discovery.

Original languageEnglish
Title of host publicationStem Cell Engineering
Subtitle of host publicationPrinciples and Applications
PublisherSpringer Berlin Heidelberg
Pages119-141
Number of pages23
ISBN (Print)9783642118647
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Cardiac differentiation
  • Conductive surfaces
  • Electrical stimulation
  • Indium-Tin-Oxide
  • Mouse embryonic stem cells
  • Multi-Electrode Assembly
  • Myosin light chain-2v
  • Optical Recording

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