Abstract
| Original language | English |
|---|---|
| Article number | e54524 |
| Number of pages | 13 |
| Journal | PLoS ONE |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes. / Raynaud, Christophe M; Halabi, Najeeb; Elliott, David Anthony; Pasquier, Jennifer; Elefanty, Andrew George; Stanley, Edouard; Rafii, Arash.
In: PLoS ONE, Vol. 8, No. 1, e54524, 2013.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes
AU - Raynaud, Christophe M
AU - Halabi, Najeeb
AU - Elliott, David Anthony
AU - Pasquier, Jennifer
AU - Elefanty, Andrew George
AU - Stanley, Edouard
AU - Rafii, Arash
PY - 2013
Y1 - 2013
N2 - 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-beta1, 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-beta1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.
AB - 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-beta1, 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-beta1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.
UR - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054524
U2 - 10.1371/journal.pone.0054524
DO - 10.1371/journal.pone.0054524
M3 - Article
VL - 8
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e54524
ER -