Human Embryonic Stem Cell Derived Mesenchymal Progenitors Express Cardiac Markers but Do Not Form Contractile Cardiomyocytes
Open Access
- 16 January 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (1), e54524
- https://doi.org/10.1371/journal.pone.0054524
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.Keywords
This publication has 45 references indexed in Scilit:
- Mesenchymal Stem Cells for Cardiac Therapy: Practical Challenges and Potential MechanismsStem Cell Reviews and Reports, 2012
- [Effect of mesenchymal stem cells on cardiac function and restenosis of injured artery after myocardial infarction].2011
- Induced bone marrow mesenchymal stem cells improve cardiac performance of infarcted rat heartsMolecular Biology Reports, 2011
- Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5‐azacytidine enhances therapeutic efficacy for myocardial infarctionBiotechnology Progress, 2010
- Myocardial oxygenation and functional recovery in infarct rat hearts transplanted with mesenchymal stem cellsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Cardiac Stem Cells in Brown Adipose Tissue Express CD133 and Induce Bone Marrow Nonhematopoietic Cells to Differentiate into CardiomyocytesThe International Journal of Cell Cloning, 2007
- Derivation of Multipotent Mesenchymal Precursors from Human Embryonic Stem CellsPLoS Medicine, 2005
- Structural and functional characterisation of cardiac fibroblastsCardiovascular Research, 2005
- Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantationThe Lancet, 2003
- Regeneration of cardiomyocytes from bone marrow: Use of mesenchymal stem cell for cardiovascular tissue engineeringCytotechnology, 2003