Journal article
Cardiopoietic programming of embryonic stem cells for tumor-free heart repair
The Journal of experimental medicine, Vol.204(2), pp.405-420
02/19/2007
DOI: 10.1084/jem.20061916
PMCID: PMC2118723
PMID: 17283208
Abstract
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-α, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF-α 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-α–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.
Details
- Title: Subtitle
- Cardiopoietic programming of embryonic stem cells for tumor-free heart repair
- Creators
- Atta Behfar - 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 55905Carmen Perez-Terzic - 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 55905Randolph S Faustino - 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 55905D. Kent Arrell - 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 55905Denice M Hodgson - 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 55905Satsuki Yamada - 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 55905Michel Puceat - 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 55905Nicolas Niederländer - 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 55905Alexey E Alekseev - 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 55905Leonid V Zingman - 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 55905Andre Terzic - 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
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.204(2), pp.405-420
- DOI
- 10.1084/jem.20061916
- PMID
- 17283208
- PMCID
- PMC2118723
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 02/19/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094401902771
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