Skip to main content
SpringerLink
Log in

Cell Therapy for Myocardial Damage

Arrhythmia Risk and Mechanisms

  • Chapter
Stem Cells And Myocardial Regeneration

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 690 Accesses

Abstract

Ischemic heart disease resulting from myocardial infarction (MI) is the leading cause of sudden cardiac death (SCD) in the United States. Recent clinical and basic science investigations have focused on replacing damaged myocardium with skeletal muscle myoblasts (SKMBs) and bone marrow-derived stem cells (BMCs). Such cell therapies for MI have been shown to improve cardiac function; however, it is unknown if electrical viability of damaged myocardium can be restored and, thus, reduce the risk for SCD. Presently, several studies suggest that SKMB therapy for damaged myocardium increases arrhythmia risk, which may be causally related to a lack of SKMB integration into the electrical syncytium of the heart. In contrast, BMCs demonstrate less arrhythmia risk, enhanced electrical viability, and evidence of electrical integration. Other cell types and delivery methods may offer an even greater potential for enhanced electrical viability and reduced arrhythmia risk. Considering that SCD associated with damaged myocardium is primarily caused by arrhythmias, it is clear that an important factor that will determine whether cell therapy will succeed or fail is its electrophysiological consequence.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
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 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 1998;4:929–933.

    Article  PubMed  CAS  Google Scholar 

  2. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701–705.

    Article  PubMed  CAS  Google Scholar 

  3. Yau TM, Tomita S, Weisel RD, et al. Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells. Ann Thorac Surg 2003;75:169–176.

    Article  PubMed  Google Scholar 

  4. Menasche P, Hagege AA, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet 2001;357:279–280.

    Article  PubMed  CAS  Google Scholar 

  5. Assmus B, Schachinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 2002;106:3009–3017.

    Article  PubMed  Google Scholar 

  6. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913–1918.

    Article  PubMed  Google Scholar 

  7. Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 2003;361:45–46.

    Article  PubMed  Google Scholar 

  8. Tse HF, Kwong YL, Chan JK, et al. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 2003;361:47–49.

    Article  PubMed  Google Scholar 

  9. Menasche P, Hagege AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003;41:1078–1083.

    Article  PubMed  Google Scholar 

  10. Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with sixmonth follow-up. J Am Coll Cardiol 2003;42:2063–2069.

    Article  PubMed  Google Scholar 

  11. Dib N, Michler RE, Pagani FD, et al. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up. Circulation 2005;112:1748–1755.

    Article  PubMed  Google Scholar 

  12. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004;364:141–148.

    Article  PubMed  Google Scholar 

  13. Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg 1995;60:12–18.

    PubMed  CAS  Google Scholar 

  14. Atkins BZ, Lewis CW, Kraus WE, et al. Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ. Ann Thorac Surg 1999;67:124–129.

    Article  PubMed  CAS  Google Scholar 

  15. Murry CE, Wiseman RW, Schwartz SM, et al. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 1996;98:2512–2523.

    Article  PubMed  CAS  Google Scholar 

  16. Zhang YM, Hartzell C, Narlow M, et al. Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. Circulation 2002;106:1294–1299.

    Article  PubMed  Google Scholar 

  17. Abraham MR, Henrikson CA, Tung L, et al. Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. Circ Res 2005;97:159–167.

    Article  PubMed  CAS  Google Scholar 

  18. Fernandes S, Amirault JC, Lande G, et al. Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias. Cardiovasc Res 2006;69:348–358.

    Article  PubMed  CAS  Google Scholar 

  19. Mills WR, Mal N, Forudi F, Popovic ZB, Penn MS, Laurita KR. Optical mapping of late myocardial infarction in rat. Am J Physiol Heart Circ Physiol 2006;290:H1298–H1306.

    Article  PubMed  CAS  Google Scholar 

  20. Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 2003;362:697–703.

    Article  PubMed  CAS  Google Scholar 

  21. Mills WR, Mal N, Kiedrowski MJ, et al. Stem cell therapy enhances electrical viability in myocardial infarction. Circulation 2005;112:247.

    Article  CAS  Google Scholar 

  22. Mills WR, Mal N, Kiedrowski MJ, et al. Does transplantation of skeletal myoblasts genetically modified to overexpress stromal-derived Factor 1 restore normal conduction in chronic ischemic heart disease? Heart Rhythm 2005;S141.

    Google Scholar 

  23. Valiunas V, Doronin S, Valiuniene L, et al. Human mesenchymal stem cells make cardiac connexins and form functional gap junctions. J Physiol 2004;555:617–626.

    Article  PubMed  CAS  Google Scholar 

  24. Laurita KR, Chuck ET, Yang TN, et al. Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. J Lab Clin Med 2003;142:83–89.

    Article  PubMed  CAS  Google Scholar 

  25. Laurita KR, Rosenbaum DS. Interdependence of modulated dispersion and tissue structure in the mechanism of unidirectional block. Circ Res 2000;87:922–928.

    PubMed  CAS  Google Scholar 

  26. Fouts K, Fernandes B, Mal N, Liu J, Laurita KR. Electrophysiological consequence of skeletal myoblast transplantation in normal and infarcted canine myocardium. Heart Rhythm 2006;3:452–461.

    Article  PubMed  Google Scholar 

  27. Krucoff MW, Crater S, Taylor DA, Soliman AM, Morimoto Y. Cell location may be a primary determinant of safety after myoblast transplantation into the infarcted heart. JACC 2004;43.

    Google Scholar 

  28. Chang M, Emokpae R, Zhang Y, et al. Co-culture of mesenchymal stem cells and neonatal rat ventricular myocytes produces an arrhythmic substrate. Heart Rhythm 2005;S48.

    Google Scholar 

  29. Reinecke H, MacDonald GH, Hauschka SD, et al. Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair. J Cell Biol. 2000;149:731–740.

    Article  PubMed  CAS  Google Scholar 

  30. Allessie MA. Circus movement in rabbit atrial muscle as a mechanism of tachycardia III. The “leading circle” concept: a new model of circus movement in cardiac tissue without the involvement of an anatomic obstacle. Circ Res 1977;41:9–18.

    PubMed  CAS  Google Scholar 

  31. Potapova I, Plotnikov A, Lu Z, et al. Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers. Circ Res 2004;94:952–959.

    Article  PubMed  CAS  Google Scholar 

  32. Abraham R, Lim P, Henrickson CA, et al. Mechanisms and potential pharmacological gene therapy strategies for myoblast transplant-associated ventricular arrhythmias: insights from a unique in vitro model. Circulation 2004;III–1.

    Google Scholar 

  33. Reinecke H, Minami E, Virag JI, et al. Gene transfer of connexin43 into skeletal muscle. Hum Gene Ther 2004;15:627–636.

    Article  PubMed  CAS  Google Scholar 

  34. Suzuki K, Brand NJ, Allen S, et al. Overexpression of connexin 43 in skeletal myoblasts: relevance to cell transplantation to the heart. J Thorac Cardiovasc Surg 2001;122:759–766.

    Article  PubMed  CAS  Google Scholar 

  35. Feld Y, Melamed-Frank M, Kehat Z, et al. Electrophysiological modulation of cardiomyocytic tissue by transfected fibroblasts expressing potassium channels-a novel strategy to manipulate excitability. Circulation 2002;105:522–529.

    Article  PubMed  CAS  Google Scholar 

  36. Xue T, Cho HC, Akar FG, et al. Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation 2005;111:11–20.

    Article  PubMed  Google Scholar 

  37. Kehat I, Khimovich L, Caspi O, et al. Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 2004;22:1282–1289.

    Article  PubMed  CAS  Google Scholar 

  38. Singla DK, Hacker TA, Ma L, et al. Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J Mol Cell Cardiol 2006;40:195–200.

    Article  PubMed  CAS  Google Scholar 

  39. Urbanek K, Rota M, Cascapera S, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and longterm survival. Circ Res 2005;97:663–673.

    Article  PubMed  CAS  Google Scholar 

  40. Wang JS, Shum-Tim D, Chedrawy E, et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications. J Thorac Cardiovasc Surg 2001;122:699–705.

    Article  PubMed  CAS  Google Scholar 

  41. Bittira B, Shum-Tim D, Al-Khaldi A, et al. Mobilization and homing of bone marrow stromal cells in myocardial infarction. Eur J Cardiothorac Surg 2003;24:393–398.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH

    William R. Mills MD & Kenneth R. Laurita PhD

Authors
  1. William R. Mills MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth R. Laurita PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bakken Heart Brain Institute and Coronary Intensive Care Unit, The Cleveland Clinic Foundation Cleveland, OH

    Marc S. Penn MD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Mills, W.R., Laurita, K.R. (2007). Cell Therapy for Myocardial Damage. In: Penn, M.S. (eds) Stem Cells And Myocardial Regeneration. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-272-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-272-4_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-664-1

  • Online ISBN: 978-1-59745-272-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation