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Cited by 477

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Stem cell differentiation requires a paracrine pathway in the heart

Behfar, Atta, Zingman, Leonid V., Hodgson, Denice M., Rauzier, Jean‐Michel, Kane, Garvan C., Terzic, Andre, Pucéat, Michel·2002·The FASEB Journal
DOI 10.1096/fj.02-0072com
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Abstract

Members of the transforming growth factor pβ (TGF‐β) superfamily‐namely, TGF‐β and BMP2—applied to undifferentiated murine embryonic stem cells up‐regulated mRNA of mesodermal (Brachyury) and cardiac specific transcription factors (Nkx2.5, MEF2C). Embryoid bodies generated from stem cells primed with these growth factors demonstrated an increased potential for cardiac differentiation with a significant increase in beating areas and enhanced myofibrillogenesis. In an environment of postmitotic cardiomyocytes, stem cells engineered to express a fluorescent protein under the control of a cardiac promoter differentiated into fluorescent ventricular myocytes beating in synchrony with host cells, a process significantly enhanced by TGF‐β or BMP2. In vitro, disruption of the TGF‐β/BMP signaling pathways by latency‐associated peptide and/or noggin prevented differentiation of stem cells. In fact, only host cells that secrete a TGF‐β family member induced a cardiac phenotype in stem cells. In vivo, transplantation of stem cells into heart also resulted in cardiac differentiation provided that TGF‐β/BMP2 signaling was intact. In infarcted myocardium, grafted stem cells differentiated into functional cardiomyocytes integrated with surrounding tissue, improving contractile performance. Thus, embryonic stem cells are directed to differentiate into cardiomyocytes by signaling mediated through TGF‐β/BMP2, a cardiac paracrine pathway required for therapeutic benefit of stem cell transplantation in diseased heart.—Behfar, A., Zingman, L. V., Hodgson, D. M., Rauzier, J.‐M., Kane, G. C., Terzic, A., Pucéat, M. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J . 16, 1558–1566 (2002)

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Metadata

Authors
Behfar, A., Zingman, L. V., Hodgson, D. M., Rauzier, J., Kane, G. C., Terzic, A., & Pucéat, M.
Venue
The FASEB Journal
Publisher
Wiley
Published
2002-10
Volume
16
Issue
12
Pages
1558-1566
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.02-0072com
OpenAlex
W1979608640
Cited by
477
References
47
FWCI
8.42
Type
journal article
Language
en
Open access
closed

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