Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells

Elisa Giacomelli, Milena Bellin, Luca Sala, Berend J. Van Meer, Leon G.J. Tertoolen, Valeria V. Orlova, Christine L. Mummery* (Corresponding Author)

*Corresponding author for this work

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Abstract

Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology in vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues in vitro that integrate both cell types in complex 3D structures. We established conditions for simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells following initial cardiac mesoderm induction. The endothelial cells expressed cardiac markers that were also present in primary cardiac microvasculature, suggesting cardiac endothelium identity. These cell populations were further enriched based on surface markers expression, then recombined allowing development of beating 3D structures termed cardiac microtissues. This in vitro model was robustly reproducible in both embryonic and induced pluripotent stem cells. It thus represents an advanced human stem cell-based platform for cardiovascular disease modelling and testing of relevant drugs.

Original languageEnglish
Pages (from-to)1008-1017
Number of pages10
JournalDevelopment (Cambridge)
Volume144
Issue number6
DOIs
Publication statusPublished - 15 Mar 2017

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Keywords

  • Cardiac microtissue (MT)
  • Human pluripotent stem cell-derived cardiomyocytes
  • Human pluripotent stem cell-derived endothelial cells
  • Mesoderm induction
  • Three-dimensional culture model

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