Human Embryonic Stem Cell Derived Mesenchymal Progenitors Express Cardiac Markers but Do Not Form Contractile Cardiomyocytes

Christophe M. Raynaud, Najeeb Halabi, David A. Elliott, Jennifer Pasquier, Andrew G. Elefanty, Edouard G. Stanley, Arash Rafii Tabrizi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs) derived in vitro from human embryonic stem cells (hESCs). Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs) efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

Original languageEnglish
Article numbere54524
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - 16 Jan 2013

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embryonic stem cells
Stem cells
Cardiac Myocytes
Genes
Mesenchymal Stromal Cells
Azacitidine
genes
Derivatives
therapeutics
stromal cells
chondrocytes
cells
heart failure
Chondrocytes
adipocytes
Adipocytes
bone marrow
stem cells
Bone
Transcription Factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Human Embryonic Stem Cell Derived Mesenchymal Progenitors Express Cardiac Markers but Do Not Form Contractile Cardiomyocytes. / Raynaud, Christophe M.; Halabi, Najeeb; Elliott, David A.; Pasquier, Jennifer; Elefanty, Andrew G.; Stanley, Edouard G.; Tabrizi, Arash Rafii.

In: PLoS One, Vol. 8, No. 1, e54524, 16.01.2013.

Research output: Contribution to journalArticle

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