Journal article
Stem cell differentiation requires a paracrine pathway in the heart
The FASEB journal, Vol.16(12), pp.1558-1566
10/2002
DOI: 10.1096/fj.02-0072com
PMID: 12374778
Abstract
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)
Details
- Title: Subtitle
- Stem cell differentiation requires a paracrine pathway in the heart
- Creators
- Atta Behfar - Mayo Clinic, Mayo FoundationLeonid V Zingman - Mayo Clinic, Mayo FoundationDenice M Hodgson - Mayo Clinic, Mayo FoundationJean‐Michel Rauzier - INSERM U390, Laboratoire de Physiopathologie CardiovasculaireGarvan C Kane - Mayo Clinic, Mayo FoundationAndre Terzic - Mayo Clinic, Mayo FoundationMichel Pucéat - Mayo Clinic, Mayo Foundation
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.16(12), pp.1558-1566
- DOI
- 10.1096/fj.02-0072com
- PMID
- 12374778
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 9
- Grant note
- Institut Federatif de Recherche JeanFrançois PECHERE (IFR24) NIH American Physicians Fellowship for Medicine in Israel Mayo Foundation Association Francaise contre les myopathies (7778) Fondation de France (2000003470) National Institutes of Health (NIH) (HL-64822; HL-07111)
- Language
- English
- Date published
- 10/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094480202771
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