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Embryonic stem cells prevent developmental cardiac defects in mice

Nature Clinical Practice Cardiovascular Medicine volume 3, pages S14–S17 (2006)Cite this article

Abstract

The potential therapeutic use of embryonic stem cells (ESCs) has gathered the attention of the scientific and medical communities recently. We report that in addition to their unique capacity to populate defective cardiac tissues, ESCs secrete factors that correct gene expression profiles in the defective neighboring cells. Id (inhibitor of DNA binding) gene knockout (KO) mouse embryos die at midgestation because of multiple cardiac defects, but injection of ESCs into preimplantation Id KO embryos prevents these defects and corrects gene expression profiles throughout the heart. ESCs injected into expectant mothers only partially rescue cardiac defects in the Id KO embryos. Two secreted factors are implicated in the rescue process: insulin-like growth factor I accounts for the long-range action of the ESCs, and Wnt5a, a short-range factor, corrects gene expression profiles in the Id KO hearts. Future studies are discussed.

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References

  1. Davani S et al. (2004) Can stem cells mend a broken heart? Cardiovasc Res 65: 305–316

    Article  Google Scholar 

  2. Mayhall EA et al. (2004) The clinical potential of stem cells. Curr Opin Cell Biol 16: 713–720

    Article  CAS  Google Scholar 

  3. Caspi O and Gepstein L (2004) Potential applications of human embryonic stem cell-derived cardiomyocytes. Ann N Y Acad Sci 1015: 285–298

    Article  Google Scholar 

  4. Fraidenraich D et al. (2004) Rescue of cardiac defects in Id knockout embryos by injection of embryonic stem cells. Science 306: 247–252

    Article  CAS  Google Scholar 

  5. Ruzinova MB and Benezra R (2003) Id proteins in development, cell cycle and cancer. Trends Cell Biol 13: 410–418

    Article  CAS  Google Scholar 

  6. Jen Y et al. (1996) Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn 207: 235–252

    Article  CAS  Google Scholar 

  7. Jen Y et al. (1997) Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis. Dev Dyn 208: 92–106

    Article  CAS  Google Scholar 

  8. Reiss K et al. (1996) Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice. Proc Natl Acad Sci USA 93: 8630–8635

    Article  CAS  Google Scholar 

  9. Adamo M et al. (1989) Insulin-like growth factor I messenger ribonucleic acids with alternative 5'-untranslated regions are differentially expressed during development of the rat. Endocrinology 124: 2737–2744

    Article  CAS  Google Scholar 

  10. Liu JP et al. (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75: 59–72

    CAS  PubMed  Google Scholar 

  11. Cadigan KM and Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11: 3286–3305

    Article  CAS  Google Scholar 

  12. Schneider VA and Mercola M (2001) Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev 15: 304–315

    Article  CAS  Google Scholar 

  13. Oishi I et al. (2003) The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 8: 645–654

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank E Stillwell and EE Romero for performing the experiments with chimeras, K Manova for assistance with the tissue histology, and CT Basson for the echocardiography studies and discussion. D Fraidenraich and R Benezra are supported by grants from the National Institutes of Health.

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Authors and Affiliations

  1. a Senior Research Scientist at, Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    Diego Fraidenraich

  2. Member of, the Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    Robert Benezra

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  1. Diego Fraidenraich
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  2. Robert Benezra
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Correspondence to Diego Fraidenraich.

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The authors declare no competing financial interests.

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Fraidenraich, D., Benezra, R. Embryonic stem cells prevent developmental cardiac defects in mice. Nat Rev Cardiol 3 (Suppl 1), S14–S17 (2006). https://doi.org/10.1038/ncpcardio0402

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  • DOI: https://doi.org/10.1038/ncpcardio0402

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