Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Behfar, A. Articles by Terzic, A. Search for Related Content PubMed PubMed Citation Articles by Behfar, A. Articles by Terzic, A. Related Collections Related Article Social Bookmarking                      What's this?

Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Department of Medical Genetics, and Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905

CORRESPONDENCE Andre Terzic: terzic.andre{at}mayo.edu

Embryonic stem cells have the distinct potential for tissue regeneration, including cardiac repair. Their propensity for multilineage differentiation carries, however, the liability of neoplastic growth, impeding therapeutic application. Here, the tumorigenic threat associated with embryonic stem cell transplantation was suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF- to promote cardiac differentiation was recapitulated in embryoid bodies in vitro. The procardiogenic action required an intact endoderm and was mediated by secreted cardio-inductive signals. Resolved TNF-–induced endoderm-derived factors, combined in a cocktail, secured guided differentiation of embryonic stem cells in monolayers produce cardiac progenitors termed cardiopoietic cells. Characterized by a down-regulation of oncogenic markers, up-regulation, and nuclear translocation of cardiac transcription factors, this predetermined population yielded functional cardiomyocyte progeny. Recruited cardiopoietic cells delivered in infarcted hearts generated cardiomyocytes that proliferated into scar tissue, integrating with host myocardium for tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone stem cell pluripotency, offering a tumor-resistant approach for regeneration.

Abbreviations used: BMP, bone morphogenetic protein; CFP, cyan fluorescence protein; EGF, epidermal growth factor; FGF, fibroblast growth factor; IGF, insulin-like growth factor; MAPK, mitogen-activated protein kinase; MEF, myocyte enhancer factor; NGF, nerve growth factor; TACE, TNF- converting enzyme; TAK, TGF-ß–activated kinase; VEGF, vascular endothelial growth factor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Tumor-free heart repair

Hema Bashyam
J. Exp. Med. 2007 204: 208a. [Full Text] [PDF]

This article has been cited by other articles:

• Nelson, T. J., Faustino, R. S., Chiriac, A., Crespo-Diaz, R., Behfar, A., Terzic, A. (2008). CXCR4+/FLK-1+ Biomarkers Select a Cardiopoietic Lineage from Embryonic Stem Cells. Stem Cells 26: 1464-1473 [Abstract] [Full Text]  
• Schenke-Layland, K., Rhodes, K. E., Angelis, E., Butylkova, Y., Heydarkhan-Hagvall, S., Gekas, C., Zhang, R., Goldhaber, J. I., Mikkola, H. K., Plath, K., MacLellan, W. R. (2008). Reprogrammed Mouse Fibroblasts Differentiate into Cells of the Cardiovascular and Hematopoietic Lineages. Stem Cells 26: 1537-1546 [Abstract] [Full Text]  
• Smart, N., Riley, P. R. (2008). The Stem Cell Movement. Circ. Res. 102: 1155-1168 [Abstract] [Full Text]  
• Crisostomo, P. R., Wang, Y., Markel, T. A., Wang, M., Lahm, T., Meldrum, D. R. (2008). Human mesenchymal stem cells stimulated by TNF-{alpha}, LPS, or hypoxia produce growth factors by an NF{kappa}B- but not JNK-dependent mechanism. Am. J. Physiol. Cell Physiol. 294: C675-C682 [Abstract] [Full Text]  
• Arrell, D. K., Niederlander, N. J., Faustino, R. S., Behfar, A., Terzic, A. (2008). Cardioinductive Network Guiding Stem Cell Differentiation Revealed by Proteomic Cartography of Tumor Necrosis Factor {alpha}-Primed Endodermal Secretome. Stem Cells 26: 387-400 [Abstract] [Full Text]  
• Behfar, A., Terzic, A. (2007). Cardioprotective repair through stem cell-based cardiopoiesis. J. Appl. Physiol. 103: 1438-1440 [Abstract] [Full Text]  
• Janssens, S. (2007). Human embryonic stem cells for cardiac repair: the focus is on refined selection and cardiopoietic programming. Heart 93: 1173-1174 [Full Text]  
• Tomescot, A., Leschik, J., Bellamy, V., Dubois, G., Messas, E., Bruneval, P., Desnos, M., Hagege, A. A., Amit, M., Itskovitz, J., Menasche, P., Puceat, M. (2007). Differentiation In Vivo of Cardiac Committed Human Embryonic Stem Cells in Postmyocardial Infarcted Rats. Stem Cells 25: 2200-2205 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS