Skip to main content
SpringerLink
Log in

Cardiac Commitment of Embryonic Stem Cells for Myocardial Repair

  • Protocol
Molecular Cardiology

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 112))

  • 638 Accesses

Abstract

Embryonic stem (ES) cells represent a source for cell-based regenerative therapies of heart failure. The pluripotency and the plasticity of ES cells allow them to be committed to a cardiac lineage following treatment with growth factors of the transforming growth factor (TGF)-β superfamily. We describe a protocol designed to turn on expression of cardiac-specific genes in undiffer entiated murine ES cells stimulated with BMP2 and/or TGF-β. Cell commit ment results in a significant improvement in spontaneous cardiac differentiation of ES cells both in vitro and in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Megeney, L. A., Kablar, B., Perry, R. L., Ying, C., May, L. and Rudnicki, M. A. (1999) Severe cardiomyopathy in mice lacking dystrophin and MyoD. Proc. Natl. Acad. Sci. USA 96, 220–225.

    Article  PubMed  CAS  Google Scholar 

  2. Schonberger, J., et al. (2001) Many roads lead to a broken heart: the genetics of dilated cardiomyopathy. Am. J. Hum. Genet. 69, 249–260.

    Article  PubMed  CAS  Google Scholar 

  3. Cox, G. and Kunkel, L. (1997) Dystrophies and heart disease. Curr. Opin. Cardiol. 12, 229–343.

    Article  Google Scholar 

  4. Scorsin, M., Marotte, F., Sabri, A., Le Dref, O., Demirag, M., Samuel, J. L., Rappaport, L., and Menasche, P. (1996) Can grafted cardiomyocytes colonize peri-infarct myocardial areas? Circulation 94, II337–1340.

    PubMed  CAS  Google Scholar 

  5. Klug, M. G., Soonpaa, M. H., Koh, G. Y. and Field, L. J. (1996) Genetically selected cardiomyocytes from differentiating embronic stem cells form stable in tracardiac grafts. J. Clin. Invest. 98, 216–224.

    Article  PubMed  CAS  Google Scholar 

  6. Leor, J., Patterson, M., Quinones, M. J., Kedes, L. H., and Kloner, R. A. (1996) Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. A potential method for repair of infarcted myocardium? Circulation 94, II332–336.

    PubMed  CAS  Google Scholar 

  7. Kessler, P. D. and Byrne, B. J. (1999) Myoblast cell grafting into heart muscle: cellular biology and potential applications. Annu. Rev. Physiol. 61, 219–242.

    Article  PubMed  CAS  Google Scholar 

  8. Roell, W., et al. (2002) Cellular cardiomyoplasty improves survival after myo cardial injury. Circulation 105, 2435–2441.

    Article  PubMed  Google Scholar 

  9. Rubart, M., Pasumarthi, K. B., Nakajima, H., Soonpaa, M. H., Nakajima, H. O., and Field, L. J. (2003) Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ. Re.s 92, 1217–1224.

    Article  CAS  Google Scholar 

  10. Beltrami, A. P., et al. (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med. 344, 1750–1757.

    Article  PubMed  CAS  Google Scholar 

  11. Scorsin, M., et al. (2000) Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J. Thorac. Cardiovasc. Surg. 119, 1169–1175.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang, M., Methot, D., Poppa, V., Fujio, Y., Walsh, K., and Murry, C. E. (2001) Cardiomyocyte grafting for cardiac repair: graft cell death and anti-death strate gies. J. Mol. Cell. Cardiol. 33, 907–921.

    Article  PubMed  CAS  Google Scholar 

  13. McDonald, J. W., Liu, X. Z., Qu, Y., Liu, S., Mickey, S. K., Turetsky, D., Gottlieb, D. I., and Choi, D. W. (1999) Transplanted embryonic stem cells survive, differ entiate and promote recovery in injured rat spinal cord. Nat. Med. 5, 1410–1412.

    Article  PubMed  CAS  Google Scholar 

  14. Brazelton, T. R., Rossi, F. M., Keshet, G. I., and Blau, H. M. (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779.

    Article  PubMed  CAS  Google Scholar 

  15. Lagasse, E., et al. (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6, 1229–1234.

    Article  PubMed  CAS  Google Scholar 

  16. Orlic, D., et al. (2001) Bone marrow cells regenerate infarcted myocardium. Na ture 410, 701–705.

    CAS  Google Scholar 

  17. Reinecke, H. and Murry, C. E. (2002) Taking the death toll after cardiomyocyte grafting: a reminder of the importance of quantitative biology. J. Mol. Cell. Cardiol. 34, 251–253.

    Article  PubMed  CAS  Google Scholar 

  18. Friedenstein, A. J., Petrakova, K. V., Kurolesova, A. I., and Frolova, G. P. (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and he matopoietic tissues. Transplantation 6, 230–247.

    Article  PubMed  CAS  Google Scholar 

  19. Prockop, D. J. (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71–74.

    Article  PubMed  CAS  Google Scholar 

  20. Pittenger, M. F., et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147.

    Article  PubMed  CAS  Google Scholar 

  21. Liechty, K. W., MacKenzie, T. C., Shaaban, A. F., Radu, A., Moseley, A. M., Deans, R., Marshak, D. R. and Flake, A. W. (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplan tation in sheep. Nat. Med. 6, 1282–1286.

    Article  PubMed  CAS  Google Scholar 

  22. Wang, J. S., Shum-Tim, D., Galipeau, J., Chedrawy, E., Eliopoulos, N. and Chiu, R. C. (2000) Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J. Thorac. Cardiovasc. Surg. 120, 999–1005.

    Article  PubMed  CAS  Google Scholar 

  23. Konieczny, S. F. and Emerson, C. P., Jr. (1984) 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination. Cell 38, 791–800.

    Article  PubMed  CAS  Google Scholar 

  24. Reyes, M. and Verfailler, C. M. (2001) Characterization of multipotent adult pro genitor cells, a subpopulation of mesenchymal stem cells. Ann. NYAcad. Sci. 938, 233–235.

    Google Scholar 

  25. Jiang, Y. E. A. (2002) Pluripotency of mesechymal stem cells derived from adult marrow Nature 870, 1–9.

    Google Scholar 

  26. Evans, M. J. and Kaufman, M. H. (1981) Establishment in culture of pluripotential cells from mouse embryos Nature 292, 154–156.

    Article  PubMed  CAS  Google Scholar 

  27. Thomson, J. A., Kalishman, J., Golos, T. G., Durning, M., Harris, C. P., Becker, R. A., and Hearn, J. P.(1995) Isolation of a primate embryonic stem cell line Proc. Natl. Acad. Sci. USA 92, 7844–7848.

    Article  PubMed  CAS  Google Scholar 

  28. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., and Jones, J. M. (1998) Embryonic stem cell lines derived from human blastocysts Science 282, 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  29. Hübner, K., et al. (2003) Derivation of oocytes from mouse embryonic stem cells. Science 300, 1251–1256.

    Article  PubMed  Google Scholar 

  30. Slack, J. (1991) From Egg to Embryo: Reginal specification in Early Development, 2nd ed., Cambridge University Press, Cambridge, England.

    Book  Google Scholar 

  31. Wolpert, L. (1989) Positional information revisited. Development 107, 3–12.

    PubMed  Google Scholar 

  32. Tam, P. P. L. and Schoenwolf, G. (1999) Cardiac fate map: lineage, allocation, morphogenetic movement and cell commitment, in Heart Development (Harvey, R. P. and Rosenthal, N., eds.), pp. 3–18.

    Google Scholar 

  33. Whitman, M. (2001) Nodal signaling in early vertebrate embryos: themes and variations. Dev. Cell 1, 605–617.

    Article  PubMed  CAS  Google Scholar 

  34. Smith, A. G. (1991) Culture and differentiation of embryonic stem cells. J. Tiss. Cult. Meth. 13, 89–94.

    Article  Google Scholar 

  35. Meyer, N., Jaconi, M., Ladopoulou, A., Fort, P., and Puceat, M. (2000) A fluores cent reporter gene as a marker for ventricular specification in ES-derived cardiac cells. FEBSLett. 478, 151–158.

    Article  CAS  Google Scholar 

  36. Pfaffl, M. W. (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 9, e45.

    Article  Google Scholar 

  37. Behfar, A., Zingman, L., Hodgson, D., Rauzier, J., Kane, G., Terzic, A., and Pucéat, M. (2002) Stem cell differentiation requires a paracrine pathway in the heart. FASEB J. 16, 1558–1566.

    Article  PubMed  Google Scholar 

  38. Boeuf, H., et al. (2001) The ribosomal S6 kinases, cAMP-responsive element binding, and STAT3 proteins are regulated by different leukemia inhibitory factor signaling pathways in mouse embryonic stem cells. J. Biol. Chem. 276, 46,204–46,211.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de Recherches de Biochimie Macromol:’eculaire, Montpellier, France

    Dana Zeineddine

  2. CNRS, Centre de Recherches de Biochimie Macromol:’eculaire, Montpellier, France

    Evangelia Papadimou, Annabelle Mery, Claudine Mènard & Michel Puc

Authors
  1. Dana Zeineddine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evangelia Papadimou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annabelle Mery
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudine Mènard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Puc
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Medicine and Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL

    Zhongjie Sun

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc.

About this protocol

Cite this protocol

Zeineddine, D., Papadimou, E., Mery, A., Mènard, C., Puc, M. (2005). Cardiac Commitment of Embryonic Stem Cells for Myocardial Repair. In: Sun, Z. (eds) Molecular Cardiology. Methods in Molecular Medicine™, vol 112. Humana Press. https://doi.org/10.1385/1-59259-879-X:175

Download citation

  • DOI: https://doi.org/10.1385/1-59259-879-X:175

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-363-3

  • Online ISBN: 978-1-59259-879-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation