Skip to main content

Stem Cells for Myocardial Repair and Regeneration: Where Are We Today?

  • Protocol
  • First Online:
Stem Cells for Myocardial Regeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 660))

Abstract

An overview for the use of stem cells for myocardial repair and regeneration is provided. The overview provides the rationale for use of stem cells in myocardial repair. Potential stem cell types and technological challenges are highlighted.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. He J., Gu D., Wu X., Reynolds K., Duan X., Yao C., Wang J., Chen C. S., Chen J., Wildman R. P., Klag M. J., and Whelton P. K. (2005) Major causes of death among men and women in China. N Engl J Med 353,1124–1134.

    Article  PubMed  CAS  Google Scholar 

  2. Thom T., Haase N., Rosamond W., Howard V.J., Rumsfeld J., Manolio T., Zheng Z. J., Flegal K., O’Donnell C., Kittner S., Lloyd-Jones D., Goff D. C. Jr., Hong Y., Adams R., Friday G., Furie K., Gorelick P., Kissela B., Marler J., Meigs J., Roger V., Sidney S., Sorlie P., Steinberger J., Wasserthiel-Smoller S., Wilson M., Wolf P. (2006) American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113, e85–151.

    Article  PubMed  Google Scholar 

  3. Naghavi M., Libby P., Falk E., Casscells S.W., Litovsky S., Rumberger J., Badimon J. J., Stefanadis C., Moreno P., Pasterkamp G., Fayad Z., Stone P. H., Waxman S., Raggi P., Madjid M., Zarrabi A., Burke A., Yuan C., Fitzgerald P. J., Siscovick D. S., de Korte C. L, Aikawa M., Juhani Airaksinen K. E., Assmann G., Becker C. R., Chesebro J. H., Farb A., Galis Z. S., Jackson C., Jang I. K., Koenig W., Lodder R. A., March K., Demirovic J., Navab M., Priori S. G., Rekhter M. D., Bahr R., Grundy S. M., Mehran R., Colombo A., Boerwinkle E., Ballantyne C., Insull W. Jr., Schwartz R. S., Vogel R., Serruys P. W., Hansson G. K., Faxon D. P., Kaul S., Drexler H., Greenland P., Muller J. E., Virmani R., Ridker P. M., Zipes D. P., Shah P. K., Willerson J. T. (2003) From vulnerable plaque to vulnerable patient. A call for new definitions and risk assessment strategies: Part I. Circulation 108, 1664–72.

    Article  PubMed  Google Scholar 

  4. Cohn J. N., Bristow M. R., Chien K. R., Colucci W. S., Frazier O. H., Leinwand L. A., Lorell B. H., Moss A. J., Sonnenblick E. H., Walsh R. A., Mockrin S. C., and Reinlib L. (1997) Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart Failure Research. Circulation 95, 766–70.

    Article  PubMed  CAS  Google Scholar 

  5. Lenfant C. (1997) Fixing the failing heart. Circulation 95, 771–2.

    Article  PubMed  CAS  Google Scholar 

  6. Mannheimer C., Camici P., Chester M. R., Collins A., DeJongste M., Eliasson T., Follath F., Hellemans I., Herlitz J., Lüscher T., Pasic M., and Thelle D. (2002) The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J 23, 355–70.

    Article  PubMed  CAS  Google Scholar 

  7. Mathur A., and Martin J. F. (2004) Stem cells and repair of the heart. Lancet 364, 183–92.

    Article  PubMed  CAS  Google Scholar 

  8. El Oakley R. M., Yonan N. A., Simpson B. M., and Deiraniya A. K. (1996) Extended criteria for cardiac allograft donors: a consensus study. J Heart Lung Transplant 15, 255–9.

    PubMed  CAS  Google Scholar 

  9. Keck B., Bennett L., Rosendale J., Daily O., Novick R., and Hosenpud J. (1999) Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT International Registry for Thoracic Organ Transplantation. Clin Transpl 35–49.

    Google Scholar 

  10. Rumyantsev P. P. (1977) Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration. Int Rev Cytol 51, 186–273.

    PubMed  CAS  Google Scholar 

  11. Dorfman J., and Kao R. L. (1997) Myocardial growth and regeneration overview. In: Chiu RC, ed. Cellular cardiomyoplasty: myocardial repair with cell implantation. Austin: Landes Bioscience, 1–25.

    Google Scholar 

  12. Mann D. L. (1999) Mechanisms and models in heart failure: A combinatorial approach. Circulation 100, 999–1008.

    Article  PubMed  CAS  Google Scholar 

  13. Beltrami A. P., Barlucchi L., Torella D., Baker M., Limana F., Chimenti S., Kasahara H., Rota M., Musso E., Urbanek K., Leri A., Kajstura J., Nadal-Ginard B., and Anversa P. (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763–76.

    Article  PubMed  CAS  Google Scholar 

  14. Urbanek K., Torella D., Sheikh F., Angelis A. D., Nurzynska D., Silvestri F., Beltrami C. A., Bussani R., Beltrami A. P., Quaini F., Bolli R., Leri A., Kajstura J., and Anversa P. (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 102, 8692–7.

    Article  PubMed  CAS  Google Scholar 

  15. Nadal-Ginard B., Kajstura J., Leri A., and Anversa P. (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92, 139–50.

    Article  PubMed  CAS  Google Scholar 

  16. Anversa P., Leri A., and Kajstura J. (2006) Cardiac regeneration. J Am Coll Cardiol 47, 1769–76.

    Article  PubMed  Google Scholar 

  17. Schuster M. D., Kocher A. A., Seki T., Martens T. P., Xiang G., Homma S., and Itescu S. (2004) Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physiol Heart Circ Physiol 287, H525–32.

    Article  PubMed  CAS  Google Scholar 

  18. Orlic D., Kajstura J., Chimenti S., Limana F., Jakoniuk I., Quaini F., Nadal-Ginard B., Bodine D. M., Leri A., and Anversa P. (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A 98, 10344–9.

    Article  PubMed  CAS  Google Scholar 

  19. Jackson K. A., Majka S. M., Wang H., Pocius J., Hartley C. J., Majesky M. W., Entman M. L., Michael L. H., Hirschi K. K., and Goodell M. A. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107, 1395–402.

    Article  PubMed  CAS  Google Scholar 

  20. Murry C. E., Reinecke H., and Pabon L. M. (2006) Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol 47, 1777–85.

    Article  PubMed  Google Scholar 

  21. Chien K. R. (2004) Stem cells: Lost in translation. Nature 428, 607.

    Article  PubMed  CAS  Google Scholar 

  22. Patel A. N., Geffner L., Vina R. F., Saslavsky J., Urschel H. C., Kormos R. and Benetti F. (2005) Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized study. J Thorac Cardiovasc Surg 130, 1631–8.

    Article  PubMed  Google Scholar 

  23. Ince H., Valgimigli M., Petzsch M., de Lezo J. S., Kuethe F., Dunkelmann S., Biondi-Zoccai G., and Nienaber C. A. (2008) Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis. Heart 94, 610–6.

    Article  PubMed  CAS  Google Scholar 

  24. Zohlnhöfer D., Ott I., Mehilli J., Schömig K., Michalk F., Ibrahim T., Meisetschläger G., von Wedel J., Bollwein H., Seyfarth M., Dirschinger J., Schmitt C., Schwaiger M., Kastrati A., Schömig A. (2006) Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction. JAMA 295, 1003–10

    Article  PubMed  Google Scholar 

  25. Ripa R. S., Jørgensen E., Wang Y., Thune J. J., Nilsson J. C., Søndergaard L., Johnsen H. E., Køber L., Grande P., and Kastrup J. (2006) Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction. Circulation 113, 1983–92.

    Article  PubMed  CAS  Google Scholar 

  26. Valgimigli M., Rigolin G. M., Cittanti C., Malagutti P., Curello S., Percoco G., Bugli A. M., Della Porta M., Bragotti L. Z., Ansani L., Mauro E., Lanfranchi A., Giganti M., Feggi L., Castoldi G., and Ferrari R. (2005) Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J 26, 1838–45.

    Article  PubMed  CAS  Google Scholar 

  27. Baxterpress release (2006) http://www.baxter.com/about_baxter/news_room/news_releases/03-07-06stem_cell_trial.html.

  28. Sinha S., Poh K. K., Sodano D., Flanagan J., Ouilette C., Kearney M., Heyd L., Wollins J, Losordo D., and Weinstein R. (2006) Safety and efficacy of peripheral blood progenitor cell mobilization and collection in patients with advanced coronary heart disease. J Clin Apher 21, 116–20.

    Article  PubMed  Google Scholar 

  29. Strauer B. E., Brehm M., Zeus T, Kostering M., Hernandez A., Sorg R. V., Kogler G., and Wernet P. (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106, 1913–8.

    Article  PubMed  Google Scholar 

  30. Tse H. F., Kwong Y. L., Chan J. K., Lo G., Ho C. L., and Lau C. P. (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361, 47–9.

    Article  PubMed  Google Scholar 

  31. Meyer G. P., Wollert K. C., Lotz J., Stgeffens J., Lippolt P., Fichtner S., Hecker H., Schaefer A., Arseniev L., Hertenstein B., Ganser A., and Drexler H. (2006) Intracoronary bone marrow cell transfer after eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrow transfer to enhance ST-elevation infarct regeneration) trial. Circulation 113,1287–94.

    Article  PubMed  Google Scholar 

  32. Assmus B., Honold J., Schächinger V., Britten M. B., Fischer-Rasokat U., Lehmann R., Teupe C., Pistorius K., Martin H., Abolmaali N. D., Tonn T., Dimmeler S., and Zeiher A. M. (2006) Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 355, 1222–32.

    Article  PubMed  CAS  Google Scholar 

  33. Schachinger V., Erbs S., Elsasser A., Haberbosch W., Hambrecht R., Holschermann H., Yu J., Corti R., Mathey D. G., Hamm C. W., Suselbeck T., Assmus B., Tonn T., Dimmeler S., and Zeiher A. M. (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355, 1210–21.

    Article  PubMed  CAS  Google Scholar 

  34. Archundia A., Aceves J. L., Lopez-Hernandez M., Alvarado M., Rodriguez E., Diaz Quiroz G., Paez A., Rojas F. M., and Montano L. F. (2005) Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction. Life Sci. 78, 279–83.

    Article  PubMed  CAS  Google Scholar 

  35. Strauer B. E., Brehm M., Zeus T., Bartsch T., Schannwell C., Antke C., Sorg R. V., Kogler G., Wernet P., Muller H. W., and Kostering M. (2005) Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol 46, 1651–8.

    Article  PubMed  Google Scholar 

  36. Schachinger V., Erbs S., Elsasser A., Haberbosch W., Hambrecht R., Holschermann H., Yu J., Corti R., Mathey D. G., Hamm C. W., Mark B., Assmus B., Tonn T., Dimmeler S. and Zeiher A. M. (2006) Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 27, 2775–83.

    Article  PubMed  Google Scholar 

  37. Janssens S., Dubois C., Bogaert J., Theunissen K., Deroose C., Desmet W., Kalantzi M., Herbots L., Sinnaeve P., Dens J., Maertens J., Rademakers F., Dymarkowski S., Gheysens O., Van Cleemput J., Bormans G., Nuyts J., Belmans A., Mortelmans L., Boogaerts M., Van de Werf F. (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367, 113–21.

    Article  PubMed  Google Scholar 

  38. Dill T., Schächinger V., Rolf A., Möllmann S., Thiele H., Tillmanns H., Assmus B., Dimmeler S., Zeiher A. M., Hamm C. (2009). Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction study (REPAIR-AMI) cardiac magnetic resonance imaging substudy. Am Heart J 157 (3), 541–7.

    Article  PubMed  Google Scholar 

  39. Almsherqi Z., and El Oakley R. (2003) Bone marrow-derived cell transplantation for acute myocardial ischemia. Circulation 107, e86–7.

    Article  PubMed  Google Scholar 

  40. Liao R., Pfister O., Jain M., and Mouquet F. (2007) The bone marrow – cardiac axis of myocardial regeneration. Prog Cardiovasc Dis 50, 18–30.

    Article  PubMed  CAS  Google Scholar 

  41. Akins R. E., Boyce R. A., Madonna M. L., Schroedl N. A., Gonda S. R., McLaughlin T. A., and Hartzell C. R. (1999) Cardiac organogenesis in vitro: reestablishment of three-dimensional tissue architecture by dissociated neonatal rat ventricular cells. Tissue Eng 5, 103–18.

    Article  PubMed  CAS  Google Scholar 

  42. Bursac N., Papadaki M., Cohen R. J., Schoen F. J., Eisenberg S. R., Carrier R., Vunjak-Novakovic G., and Freed L. E. (1999) Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies. Am J Physiol 277, H433–44.

    PubMed  CAS  Google Scholar 

  43. Carrier R. L., Papadaki M., Rupnick M., Schoen F. J, Bursac N., Langer R., Freed L. E., and Vunjak-Novakovic G. (1999) Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization. Biotechnol Bioeng 64, 580–9.

    Article  PubMed  CAS  Google Scholar 

  44. Li R. K., Jia Z. Q., Weisel R. D., Mickle D. A., Choi A., and Yau T. M. (1999) Survival and function of bioengineered cardiac grafts. Circulation 100, II63–9.

    PubMed  CAS  Google Scholar 

  45. Fink C., Ergun S., Kralisch D, Remmers U., Weil J., and Eschenhagen T. (2000) Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement. FASEB J 14, 669–79.

    PubMed  CAS  Google Scholar 

  46. Leor J., Aboulafia-Etzion S., Dar A., Shapiro L., Barbash I. M., Battler A., Granot Y., and Cohen S. (2000) Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium? Circulation 102, 56–61.

    Article  PubMed  CAS  Google Scholar 

  47. Li R. K., Yau T. M., Weisel R. D., Mickle D. A., Sakai T., Choi A., and Jia Z. Q. (2000) Construction of a bioengineered cardiac graft. J Thorac Cardiovasc Surg 119, 368–75.

    Article  PubMed  CAS  Google Scholar 

  48. Zimmermann W. H., Fink C., Kralisch D., Remmers U., Weil J., and Eschenhagen T. (2000) Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol Bioeng 68, 106–14.

    Article  PubMed  CAS  Google Scholar 

  49. Eschenhagen T., Didie M., Heubach J., Ravens U., and Zimmermann W. H. (2002) Cardiac tissue engineering. Transpl Immunol 9, 315–21.

    Article  PubMed  CAS  Google Scholar 

  50. Kofidis T., Akhyari P., Boublik J., Theodorou P., Martin U., Ruhparwar A., Fischer S., Eschenhagen T., Kubis H. P., Kraft T., Leyh R., and Haverich A. (2002) In vitro engineering of heart muscle: artificial myocardial tissue. J Thorac Cardiovasc Surg 124, 63–9.

    Article  PubMed  CAS  Google Scholar 

  51. Krupnick A. S., Kreisel D., Engels F. H., Szeto W. Y., Plappert T., Popma S. H., Flake A. W., and Rosengard B. R. (2002) A novel small animal model of left ventricular tissue engineering. J Heart Lung Transplant 21, 233–43.

    Article  PubMed  Google Scholar 

  52. Shimizu T., Yamato M., Isoi Y., Akutsu T., Setomaru T., Abe K., Kikuchi A., Umezu M., and Okano T. (2002) Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res 90, e40.

    Article  PubMed  CAS  Google Scholar 

  53. Zimmermann W. H., Schneiderbanger K., Schubert P., Didie M., Munzel F., Heubach J. F., Kostin S., Neuhuber W. L., and Eschenhagen T. (2002) Tissue engineering of a differentiated cardiac muscle construct. Circ Res 90, 223–30.

    Article  PubMed  CAS  Google Scholar 

  54. Eschenhagen T., Didie M., Munzel F., Schubert P., Schneiderbanger K., and Zimmermann W. H. (2002) 3D engineered heart tissue for replacement therapy Basic Res Cardiol 97, I146–52.

    Article  PubMed  Google Scholar 

  55. Zimmermann W. H., Didie M., Wasmeier G. H., Nixdorff U., Hess A., Melnychenko I., Boy O., Neuhuber W. L., Weyand M., and Eschenhagen T. (2002) Cardiac grafting of engineered heart tissue in syngenic rats Circulation 106, I151–7.

    PubMed  Google Scholar 

  56. Kellar R. S., Landeen L. K., Shepherd B. R., Naughton G. K., Ratcliffe A., and Williams S. K. (2001) Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue. Circulation 104, 2063–8.

    Article  PubMed  CAS  Google Scholar 

  57. Vacanti J. P., Langer R., Upton J., and Marler J. J. (1998) Transplantation of cells in matrices for tissue regeneration. Adv Drug Deliv Rev 33, 165–82.

    Article  PubMed  Google Scholar 

  58. Zimmermann W. H., and Eschenhagen T. (2003) Cardiac tissue engineering for replacement therapy. Heart Fail Rev 8, 259–69.

    Article  PubMed  CAS  Google Scholar 

  59. Eschenhagen T., Fink C., Remmers U., Scholz H., Wattchow J., Weil J., Zimmermann W., Dohmen H. H., Schafer H., Bishopric N., Wakatsuki T., and Elson E. L. (1997) Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB J 11, 683–94.

    PubMed  CAS  Google Scholar 

  60. Christman K. L., and Lee R. J. (2006) Biomaterials for the treatment of myocardial infarction. J Am Coll Cardiol 48, 907–13.

    Article  PubMed  CAS  Google Scholar 

  61. Zammaretti P., and Jaconi M. (2004) Cardiac tissue engineering: regeneration of the wounded heart. Curr Opin Biotechnol 15, 430–4.

    Article  PubMed  CAS  Google Scholar 

  62. Leri A., Kajstura J., Anversa P., and Frishman W. H. (2008) Myocardial regeneration and stem cell repair. Curr Probl Cardiol 33, 91–153.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Randall J. Lee MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Lee, R.J. (2010). Stem Cells for Myocardial Repair and Regeneration: Where Are We Today?. In: Lee, R. (eds) Stem Cells for Myocardial Regeneration. Methods in Molecular Biology, vol 660. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-705-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-705-1_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-704-4

  • Online ISBN: 978-1-60761-705-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics