Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Progress
  • Published:

Potential of stem-cell-based therapies for heart disease

A Corrigendum to this article was published on 23 November 2006

Abstract

The use of stem cells to generate replacement cells for damaged heart muscle, valves, vessels and conduction cells holds great potential. Recent identification of multipotent progenitor cells in the heart and improved understanding of developmental processes relevant to pluripotent embryonic stem cells may facilitate the generation of specific types of cell that can be used to treat human heart disease. Secreted factors from circulating progenitor cells that localize to sites of damage may also be useful for tissue protection or neovascularization. The exciting discoveries in basic science will require rigorous testing in animal models to determine those most worthy of future clinical trials.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Differentiation of embryonic cells into the cardiac lineage.
Figure 2: Potential of postnatal cardiac progenitor cells (CPCs).

Similar content being viewed by others

References

  1. American Heart Association in Heart Disease and Stroke Statistics—2004 Update 11–14 (American Heart Association, Dallas, Texas, 2004).

  2. Oh, H. et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl Acad. Sci. USA 100, 12313–12318 (2003).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Beltrami A. P. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763–776 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Martin, C. M. et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev. Biol. 265, 262–275 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Shim, W. S. et al. Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem. Biophys. Res. Commun. 324, 481–488 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Urbanek, K. et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ. Res. 97, 663–673 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Boiani, M. & Scholer, H. R. Regulatory networks in embryo-derived pluripotent stem cells. Nature Rev. Mol. Cell Biol. 6, 872–884 (2005).

    Article  CAS  Google Scholar 

  8. Kitajima, S., Takagi, A., Inoue, T. & Saga, Y. MesP1 and MesP2 are essential for the development of cardiac mesoderm. Development 127, 3215–3226 (2000).

    CAS  PubMed  Google Scholar 

  9. Wilson, V. & Beddington, R. Expression of T protein in the primitive streak is necessary and sufficient for posterior mesoderm movement and somite differentiation. Dev. Biol. 192, 45–58 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Buckingham, M., Meilhac, S. & Zaffran, S. Building the mammalian heart from two sources of myocardial cells. Nature Rev. Genet. 6, 826–835 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Cai, C. L. et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev. Cell 5, 877–889 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Laugwitz, K. L. et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433, 647–653 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sachinidis, A. et al. Cardiac specific differentiation of mouse embryonic stem cells. Cardiovasc. Res. 58, 278–291 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Pal, R. & Khanna, A. Role of Smad- and Wnt-dependent pathways in embryonic cardiac development. Stem Cells Dev. 15, 29–39 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Zhao, Y., Samal, E. & Srivastava, D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436, 214–220 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  16. Kwon, C., Han, Z., Olson, E. N. & Srivastava, D. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc. Natl Acad. Sci. USA 102, 18986–18991 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ding, S. & Schultz, P. G. A role for chemistry in stem cell biology. Nature Biotechnol. 22, 833–840 (2004).

    Article  CAS  Google Scholar 

  18. Laflamme, M. A. & Murry, C. E. Regenerating the heart. Nature Biotechnol. 23, 845–856 (2005).

    Article  CAS  Google Scholar 

  19. Orlic, D. et al. Bone marrow cells regenerate infarcted myocardium. Nature 410, 701–705 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Murry, C. E. et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428, 664–668 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Balsam, L. B. et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 428, 668–673 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Nygren, J. M. et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Med. 10, 494–501 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Mangi, A. A. et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nature Med. 9, 1195–1201 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Leri, A., Kajstura, J. & Anversa, P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol. Rev. 85, 1373–1416 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Janssens, S. et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367, 113–121 (2006).

    Article  PubMed  Google Scholar 

  26. Orlic, D. et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. Natl Acad. Sci. USA 98, 10344–10349 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zohlnhofer, D. et al. Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. J. Am. Med. Assoc. 295, 1003–1010 (2006).

    Article  Google Scholar 

  28. Gnecchi, M. et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 20, 661–669 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Silva, W. A. Jr et al. The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells 21, 661–669 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Bock-Marquette, I., Saxena, A., White, M. D., Dimaio, J. M. & Srivastava, D. Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 432, 466–472 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Grant, D. S. et al. Thymosin β4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 3, 125–135 (1999).

    Article  CAS  PubMed  Google Scholar 

  32. Malinda, K. M., Goldstein, A. L. & Kleinman, H. K. Thymosin β4 stimulates directional migration of human umbilical vein endothelial cells. FASEB J. 11, 474–481 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. Menasche, P. et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J. Am. Coll. Cardiol. 41, 1078–1083 (2003).

    Article  PubMed  Google Scholar 

  34. Brambrink, T., Hochedlinger, K., Bell, G. & Jaenisch, R. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. Proc. Natl Acad. Sci. USA 103, 933–938 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cowan, C. A., Atienza, J., Melton, D. A. & Eggan, K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cell. Science 309, 1369–1373 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank K. Cordes for help in conceiving and generating the graphics. K.I. is a scholar of the California Institute of Regenerative Medicine. D.S. is supported by grants from the National Heart, Lung and Blood Institute, the National Institutes of Health and the March of Dimes Birth Defects Foundation, and is an Established Investigator of the American Heart Association.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deepak Srivastava.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Author Information Reprints and permissions information is available at npg.nature.com/reprintsandpermissions.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Srivastava, D., Ivey, K. Potential of stem-cell-based therapies for heart disease. Nature 441, 1097–1099 (2006). https://doi.org/10.1038/nature04961

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04961

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing