Advertisement

Stem Cells in Cardiovascular Disease

Methods and Protocols
  • Marc S. Penn
  • Niladri Mal
Part of the Methods in Molecular Medicine book series (MIMM, volume 129)

Abstract

Stem cells are cells capable of proliferation, self-renewal, and differentiation into various organ-specific cell types. Stem cells are subclassified based on their species of origin (mice, rat, human), developmental stage of the species (embryonic, fetal, or adult), tissue of origin (hematopoietic, mesenchymal, skeletal, neural), and potential to differentiate into one or more specific types of mature cells (totipotent, pluripotent, multipotent). Embryonic stem (ES) cells are totipotent, primitive cells derived from the embryo that have the potential to become all specialized cell types. Conversely, adult stem cells are undifferentiated cells found in differentiated tissue that retain the potential to renew themselves and differentiate to yield organ-specific tissues. Stem cells are attractive candidates for novel therapeutics for patients with different heart diseases, including congestive heart failure, most commonly caused by myocardial infarction. The remarkable proliferative and differentiation capacity of stem cells promises an almost unlimited supply of specific cell types including viable functioning cardiomyocytes to replace the scarred myocardium following transplantation.

Key Words

Stem cells myocardial infarction heart failure therapeutics 

References

  1. 1.
    Pera, M. F., Reubinoff, B., and Trounson, A. (2000) Human embryonic stem cells. J. Cell. Sci. 113, 5–10.PubMedGoogle Scholar
  2. 2.
    Wognum, A. W., Eaves, A. C., and Thomas, T. E. (2003) Identification and isolation of hematopoietic stem cells. Arch. Med. Res. 34, 461–475.PubMedCrossRefGoogle Scholar
  3. 3.
    Scharenberg, C. W., Harkey, M. A., and Torok-Storb, B. (2002) The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99, 507–512.PubMedCrossRefGoogle Scholar
  4. 4.
    Di Nicola, M., Carlo-Stella, C., Magni, M., et al. (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838–3843.PubMedCrossRefGoogle Scholar
  5. 5.
    Morrison, S. J., Prowse, K. R., Ho, P., and Weissman, I. L. (1996) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5, 207–216.PubMedCrossRefGoogle Scholar
  6. 6.
    Urbich, C. and Dimmeler, S. (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ. Res. 95, 343–353.PubMedCrossRefGoogle Scholar
  7. 7.
    Beltrami, A. P., Barlucchi, L., Torella, D., et al. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763–776.PubMedCrossRefGoogle Scholar
  8. 8.
    MacCalman, C. D., Bardeesy, N., Holland, P. C., and Blaschuk, O. W. (1992) Noncoordinate developmental regulation of N-cadherin, N-CAM, integrin, and fibronectin mRNA levels during myoblast terminal differentiation. Dev. Dyn. 195, 127–132.PubMedGoogle Scholar
  9. 9.
    Messina, E., De Angelis, L., Frati, G., et al. (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res. 95, 911–921.PubMedCrossRefGoogle Scholar
  10. 10.
    Oh, H., Bradfute, S. B., Gallardo, T. D., et al. (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. USA. 100, 12,313–12,318.PubMedCrossRefGoogle Scholar
  11. 11.
    Jakobsson, J., Rosenqvist, N., Thompson, L., Barraud, P., and Lundberg, C. (2004) Dynamics of transgene expression in a neural stem cell line transduced with entiviral vectors incorporating the cHS4 insulator. Exp. Cell Res. 298, 611–623.PubMedCrossRefGoogle Scholar
  12. 12.
    Hu, M., Krause, D., Greaves, M., et al. (1997) Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev. 11, 774–785.PubMedCrossRefGoogle Scholar
  13. 13.
    Gould, S. J. and Subramani, S. (1988) Firefly luciferase as a tool in molecular and cell biology. Anal. Biochem. 175, 5–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Fraser, S. E. (1996) Lontophoretic dye labeling of embryonic cells. Methods Cell Biol. 51, 147–160.PubMedCrossRefGoogle Scholar
  15. 15.
    Jaiswal, J. K., Mattoussi, H., Mauro, J. M., and Simon, S. M. (2003) Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat. Biotechnol. 21, 47–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Osawa, M., Hanada, K., Hamada, H., and Nakauchi, H. (1996) Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273, 242–245.PubMedCrossRefGoogle Scholar
  17. 17.
    Zou, Y. R., Kottmann, A. H., Kuroda, M., Taniuchi, I., and Littman, D. R. (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393, 595–599.PubMedCrossRefGoogle Scholar
  18. 18.
    Combadiere, C., Ahuja, S. K., Van Damme, J., Tiffany, H. L., Gao, J. L., and Murphy, P. M. (1995) Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B. J. Biol. Chem. 270, 29,671–29,675.PubMedCrossRefGoogle Scholar
  19. 19.
    Laverriere, A. C., MacNeill, C., Mueller, C., Poelmann, R. E., Burch, J. B., and Evans, T. (1994) GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J. Biol. Chem. 269, 23,177–23,184.PubMedGoogle Scholar
  20. 20.
    Schott, J. J., Benson, D. W., Basson, C. T., et al. (1998) Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281, 108–111.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartz, R. J. and Olson, E. N. (1999) Building the heart piece by piece: modularity of cis-elements regulating Nkx2-5 transcription. Development 126, 4187–4192.PubMedGoogle Scholar
  22. 22.
    Yu, Y. T., Breitbart, R. E., Smoot, L. B., Lee, Y., Mahdavi, V., and Nadal-Ginard, B. (1992) Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. Genes Dev. 6, 1783–1798.PubMedCrossRefGoogle Scholar
  23. 23.
    Ausoni, S., Campione, M., Picard, A., et al. 1994. Structure and regulation of the mouse cardiac troponin I gene. J. Biol. Chem. 269, 339–346.Google Scholar
  24. 24.
    Potter, J. D., Sheng, Z., Pan, B. S., and Zhao, J. (1995) A direct regulatory role for troponin T and a dual role for troponin C in the Ca2+ regulation of muscle contraction. J. Biol. Chem. 270, 2557–2562.PubMedCrossRefGoogle Scholar
  25. 25.
    Linhares, V. L., Almeida, N. A., Menezes, D. C., et al. (2004) Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovasc. Res. 64, 402–411.PubMedCrossRefGoogle Scholar
  26. 26.
    Verheule, S., van Batenburg, C. A., Coenjaerts, F. E., Kirchhoff, S., Willecke, K., and Jongsma, H. J. (1999) Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40. J. Cardiovasc. Electrophysiol. 10, 1380–1389.PubMedCrossRefGoogle Scholar
  27. 27.
    Verheule, S., van Batenburg, C. A., Coenjaerts, F. E., Kirchhoff, S., Willecke, K., and Jongsma, H. J. (1999) Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40. J. Cardiovasc. Electrophysiol. 10, 1380–1389.PubMedCrossRefGoogle Scholar
  28. 28.
    Askari, A. T., Unzek, S., Popovic, Z. B., et al. (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362, 697–703.PubMedCrossRefGoogle Scholar
  29. 29.
    Mangi, A. A., Noiseux, N., Kong, D., et al. (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat. Med. 9, 1195–1201.PubMedCrossRefGoogle Scholar
  30. 30.
    Baschong, W., Suetterlin, R., and Laeng, R. H. (2001) Control of autofluorescence of archival formaldehyde-fixed, paraffin-embedded tissue in confocal laser scanning microscopy (CLSM). J. Histochem. Cytochem. 49, 1565–1572.PubMedGoogle Scholar
  31. 31.
    Hardeman, E. C., Chiu, C. P., Minty, A., and Blau, H. M. (1986) The pattern of actin expression in human fibroblast x mouse muscle heterokaryons suggests that human muscle regulatory factors are produced. Cell 47, 123–130.PubMedCrossRefGoogle Scholar
  32. 32.
    Yoon, Y. S., Park, J. S., Tkebuchava, T., Luedeman, C., and Losordo, D. W. (2004) Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation 109, 3154–3157.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Marc S. Penn
    • 1
  • Niladri Mal
    • 1
  1. 1.Departments of Cardiovascular Medicine and Cell BiologyThe Cleveland Clinic FoundationCleveland

Personalised recommendations