Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes

Christophe M Raynaud, Najeeb Halabi, David Anthony Elliott, Jennifer Pasquier, Andrew George Elefanty, Edouard Stanley, Arash Rafii

Research output: Contribution to journalArticleResearchpeer-review

23 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-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.
Original languageEnglish
Article numbere54524
Number of pages13
JournalPLoS ONE
Volume8
Issue number1
DOIs
Publication statusPublished - 2013

Cite this

Raynaud, Christophe M ; Halabi, Najeeb ; Elliott, David Anthony ; Pasquier, Jennifer ; Elefanty, Andrew George ; Stanley, Edouard ; Rafii, Arash. / Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes. In: PLoS ONE. 2013 ; Vol. 8, No. 1.
@article{fa4bc120fcad427c80f7854f32a742cc,
title = "Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes",
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-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.",
author = "Raynaud, {Christophe M} and Najeeb Halabi and Elliott, {David Anthony} and Jennifer Pasquier and Elefanty, {Andrew George} and Edouard Stanley and Arash Rafii",
year = "2013",
doi = "10.1371/journal.pone.0054524",
language = "English",
volume = "8",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

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 journalArticleResearchpeer-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 -