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Stem Cell Reviews and Reports

, Volume 8, Issue 2, pp 494–502 | Cite as

Stem Cells in the Treatment of Cardiovascular Disease—An Overview

  • Amita J. Hotkar
  • Warren Balinsky
Article

Abstract

CVD irreversibly damage the cardiomyocytes, the heart muscle cells. This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells, leading to heart failure and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is a potentially new strategy to treat heart failure and various other CVD. Stem cells are promising new therapeutics for patients with different heart diseases. The remarkable proliferative and differentiation capacity of stem cells promises an unlimited supply of specific cell types including viable functioning heart muscle cells. A crucial issue in designing more rational cell-based therapy approaches for cardiac disease is understanding the mechanisms by which each of the stem cell or progenitor-cell types can affect myocardial performance. This paper will highlight findings of multiple preliminary clinical experiments involving stem cells as therapeutics, educate the reader on the incidence and prevalence of CVD, the risk factors associated with CVD, and explore some of the challenges that can be encountered.

Keywords

Cardiovascular disease Cardiac regeneration Embryonic stem cells Adult stem cells Neovascularization Cell therapy 

Notes

Statement of Interest

The Authors declare no potential conflicts of interest.

References

  1. 1.
    Strelchenko, N., Verlinsky, O., Kukharenko, V., & Verlinsky, Y. (2004). Morula-derived human embryonic stem cells. Reproductive Biomedicine Online, 9(6), 623–629.PubMedCrossRefGoogle Scholar
  2. 2.
  3. 3.
    WHO. (2002). In C. Murray & A. Lopez (Eds.), World health report: Reducing risks, promoting healthy life. France: World Health Organization.Google Scholar
  4. 4.
    Chockalingam, A., & Balaguer-Vintro. (2003). Impending global pandemic of cardiovascular diseases: challenges and opportunities for the prevention and control of cardiovascular diseases in developing countries and economies in transition. World Heart Federation. Barcelona: Prous Science.Google Scholar
  5. 5.
    American Heart Association (2010). Cardiovascular Disease Cost, 2009. http://www.americanheart.org/presenter.jhtml?identifier=4475. Accessed May 5, 2010.
  6. 6.
    Wert, G., & Mummery, C. (2003). Human embryonic stem cells: Research, ethics and policy. Human Reproduction, 18(4), 672–682.PubMedCrossRefGoogle Scholar
  7. 7.
    Juengst, E., & Fossel, M. (2000). The ethics of embryonic stem cells- now and forever, cells without end. JAMA, 284(24), 3180–3184.PubMedCrossRefGoogle Scholar
  8. 8.
    Muller-Ehmsen, J., Whittaker, P., Kloner, R., Dow, J., et al. (2002). Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. Journal of Molecular and Cellular Cardiology, 34, 107.PubMedCrossRefGoogle Scholar
  9. 9.
    Chester, R., & Sackstein, R. (2010). Embryonic stem cell-based therapeutics: Balancing scientific progress and bioethics. Health Matrix: Journal of Law-Medicine, 20(1–15), 91.Google Scholar
  10. 10.
    Mummery, C., Oostwaard, D., Doevendans, P., et al. (2003). Differentiation of human embryonic stem cells to cardiomyocytes. Circulation. doi: 10.1161/01.
  11. 11.
    Kehat, I., Dorit, K., Mirit, S., et al. (2001). Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. The Journal of Clinical Investigation, 108(3), 407–414.PubMedGoogle Scholar
  12. 12.
    Mummery, C., & Robert, P. (2003). Origin and use of embryonic and adult stem cells in differentiation and tissue repair. Oxford Journal, Medicine cardiovascular research, 58(2), 324–335.Google Scholar
  13. 13.
    Hochedlinger, K., & Jaenisch, R. (2003). Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. The New England Journal of Medicine, 349(3), 275–286.PubMedCrossRefGoogle Scholar
  14. 14.
    Kawase, E. (2000). Mouse embryonic stem cell lines established from neuronal cell derived cloned blastocysts. Genesis, 28(3), 156.PubMedCrossRefGoogle Scholar
  15. 15.
    Katja, S., & MacLellan, R. (2009). Induced pluripotent stem cells: It’s like déjà vu all over again. Circulation, 120(1), 1462–1464.CrossRefGoogle Scholar
  16. 16.
    Tong, Ng Y., & Ng, S. (2002). Somatic cell nuclear transfer (Cloning): Implications for the medical practitioner. Singapore Medical Journal, 43(7), 369–376.PubMedGoogle Scholar
  17. 17.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.PubMedCrossRefGoogle Scholar
  18. 18.
    Hochedlinger, K., & Plath, K. (2009). Epigenetic reprogramming and induced pluripotency. Development, 136, 509–523.PubMedCrossRefGoogle Scholar
  19. 19.
    Shin-ichi, N., et al. (2008). The promise of human induced pluripotent stem cells for research and therapy. Nature Reviews. Molecular Cell Biology, 9(9), 725–729.CrossRefGoogle Scholar
  20. 20.
    Yu, J., Hu, K., Smuga-Otto, K., et al. (2009). Human induced pluripotent stem cells free of vector and transgene sequences. Science, 324, 797–801.PubMedCrossRefGoogle Scholar
  21. 21.
    Schenke-Layland, K., Rhodes, K., & Angelis, E. (2008). Reprogrammed mouse fibroblasts differentiate into cells of the cardiovascular and hematopoietic lineages. Stem Cells, 26, 1537–1546.PubMedCrossRefGoogle Scholar
  22. 22.
    Mauritz, C., Schwanke, K., Reppel, M., et al. (2008). Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation, 118, 507–517.PubMedCrossRefGoogle Scholar
  23. 23.
    Narazaki, G., Uosaki, H., Teranishi, M., et al. (2008). Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation, 118, 498–506.PubMedCrossRefGoogle Scholar
  24. 24.
    Zwi, L., Caspi, O., Arbel, G., et al. (2009). Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation, 120, 1513–1523.PubMedCrossRefGoogle Scholar
  25. 25.
    Freund, C., Davis, R. P., Gkatzis, K., et al. (2010). The first reported generation of human induced pluripotent stem cells (iPS cells) and iPS cell-derived cardiomyocytes in the Netherlands. Netherlands Heart Journal, 18(1), 51–54.PubMedGoogle Scholar
  26. 26.
    Zhao, T., Zhang, Z. N., Rong, Z., et al. (2011). Immunogenicity of induced pluripotent stem cells. Nature. doi: 10.1038/nature10135.
  27. 27.
    Chun, Y. S., Chaudhari, P., & Jang, Y. Y. (2010). Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease. International Journal of Biological Sciences, 6, 796–805.PubMedCrossRefGoogle Scholar
  28. 28.
    Laflamme, et al. (2007). Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nature Biotechnology, 9, 1015–1024.CrossRefGoogle Scholar
  29. 29.
    Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings of the National Academy of Sciences of the United States of America, 98, 10344.PubMedCrossRefGoogle Scholar
  30. 30.
    Seiler, C., Pohl, T., Wustmann, K., et al. (2001). Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study. Circulation, 104, 2012.PubMedCrossRefGoogle Scholar
  31. 31.
    Vasa, M., Fichtlscherer, S., Adler, K., et al. (2001). Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. American Heart Association, 103, 2885–2890.Google Scholar
  32. 32.
    Asahara, T., Murohara, T., Sullivan, A., et al. (1997). Isolation of putative endothelial progenitor cells for angiogenesis. Science, 275, 964–967.PubMedCrossRefGoogle Scholar
  33. 33.
    Lin, Y., Weisdorf, D., & Solovey, A. (2000). Origins of circulating endothelial cells and endothelial outgrowth from blood. The Journal of Clinical Investigation, 105, 71–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Kocher, A., Schuster, M., et al. (2001). Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nature Medicine, 7, 430–436.PubMedCrossRefGoogle Scholar
  35. 35.
    Huang Ngan, F., & Song, L. (2008). Mesenchymal stem cells for vascular regeneration. Regenerative Medicine, 3(6), 877–892.PubMedCrossRefGoogle Scholar
  36. 36.
    Pittenger, M. F., & Martin, B. J. (2004). Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation Research, 95, 9–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Pittenger, M. F., & Mosca, J. D. (2000). Human mesenchymal stem cells: progenitor cells for cartilage, bone, fat and stroma. Current Topics in Microbiology and Immunology, 251, 3–11.PubMedCrossRefGoogle Scholar
  38. 38.
    Toma, C., Pittenger, M. F., Cahill, K., et al. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105, 93–98.PubMedCrossRefGoogle Scholar
  39. 39.
    Devine, S., Bartholomew, A., Mahmud, N., et al. (2001). Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. ExpHematol., 29, 244–255.Google Scholar
  40. 40.
    Ferrari, M., Corradi, A., Lazzaretti, M., et al. (2007). Adult stem cells: Perspectives for therapeutic applications. Veterinary Research Communications, 31(1), 1–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Min, J. Y., Sullivan, M. F., Yang, Y., Zhang, J. P., Converso, K. L., Morgan, J. P., et al. (2002). Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. The Annals of Thoracic Surgery, 74, 1568.PubMedCrossRefGoogle Scholar
  42. 42.
    Shake, J., Gruber, P., & Baumgartner, W. (2003). Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. The Annals of Thoracic Surgery, 73, 1919.CrossRefGoogle Scholar
  43. 43.
    Thompson, C., Nasseri, B., Makower, J., et al. (2003). Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation. Journal of the American College of Cardiology, 41, 1964.PubMedCrossRefGoogle Scholar
  44. 44.
    Ankrum, J., & Karp, J. M. (2010). Mesenchymal stem cell therapy: Two steps forward, one step back. Trends in Molecular Medicine, 16(5), 203–209.PubMedCrossRefGoogle Scholar
  45. 45.
    Strauer, B., Brehm, M., & Zeus, T. (2001). Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction. Deutsche Medizinische Wochenschrift, 126, 932–938.PubMedCrossRefGoogle Scholar
  46. 46.
    Therapeutics daily newsletter (2010). http://www.bioheartinc.com. Accessed April 27, 2010.
  47. 47.
  48. 48.
    Stem Cell Therapeutics Laboratory at Cedars Sinai Hospital (2010). http://www.cedars-sinai.edu/Research-and-Education/Research-Labs/Stem-Cell-Therapeutics-Laboratory.aspx. Accessed January 2, 2011.
  49. 49.
    Laflamme, M., & Murry, C. (2005). Regenerating the heart. Nature Biotechnology, 23, 845–856.PubMedCrossRefGoogle Scholar
  50. 50.
    Kattman, S. J., Witty, A. D., Gagliardi, M., et al. (2011). Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell, 8(2), 228–240.PubMedCrossRefGoogle Scholar
  51. 51.
    Fernandes, S., Naumova, A., Zhu, W., et al. (2010). Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats. Journal of Molecular and Cellular Cardiology, 249(6), 941–949.CrossRefGoogle Scholar
  52. 52.
    Terrovitis, J., Smith, R., & Marbán, E. (2008). Assessment and optimization of cell engraftment after transplantation into the heart. Circulation Research, 106, 479–494.CrossRefGoogle Scholar
  53. 53.
    Chin, M., Mason, M., Xie, W., et al. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell, 5, 111–123.PubMedCrossRefGoogle Scholar
  54. 54.
    Cao, F., Wagner, R., Wilson, K., et al. (2008). Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PloS One, 3, e3474.PubMedCrossRefGoogle Scholar
  55. 55.
    Menasche, P., Alfieri, O., Janssens, S., McKenna, W., Reichenspurner, H., Trinquart, L., et al. (2008). The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: First randomized placebo-controlled study of myoblast transplantation. Circulation, 117(9), 1189–1200.PubMedCrossRefGoogle Scholar
  56. 56.
    Burridge, P. W., Thompson, S., Millrod, M. A., et al. (2011). A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PloS One, 6(4).Google Scholar
  57. 57.
    Hagege, A. A., Marolleau, J. P., Vilquin, J. T., Alheritiere, A., Peyrard, S., Duboc, D., et al. (2006). Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients. Circulation, 114(1), 108–113.CrossRefGoogle Scholar
  58. 58.
    Siminiak, T., Kalawski, R., Fiszer, D., Jerzykowska, O., Rzezniczak, J., Rozwadowska, N., et al. (2004). Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: Phase I clinical study with 12 months of follow-up. American Heart Journal, 148(3), 531–537.PubMedCrossRefGoogle Scholar
  59. 59.
    Amariglio, N., Hirshberg, A., Scheithauer, B., et al. (2009). Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Medicine, 6, 1000029.CrossRefGoogle Scholar
  60. 60.
    NIH timeline (2011). http://www.nih.gov/about/director/stemcell/stay_08312010.pdf. Accessed January 21, 2011.
  61. 61.
    National Institute of Health Resources for Stem Cell Research. Stem cell Information. http://stemcells.nih.gov/. Accessed June 2, 2011.
  62. 62.
    Crooks, V. A., & Snyder, J. (2010). Regulating medical tourism. Lancet, 376(9751), 1465–1466.PubMedCrossRefGoogle Scholar
  63. 63.
    Barclay, E. (2009). Stem-cell experts raise concerns about medical tourism. Lancet, 373(9667), 883–884.PubMedCrossRefGoogle Scholar
  64. 64.
    Touchette, N. (2003). Stem Cell Transplants for the Heart Face Uncertainties. http://www.genomenewsnetwork.org/articles/11_03/heart_stem_cells.shtml. Accessed May 5, 2010.

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.The Milano School of Management and Urban PolicyNew School UniversityNew YorkUSA
  2. 2.School of Management and Urban PolicyNew School UniversityNew YorkUSA

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