Skip to main content
SpringerLink
Log in

Strategies for Cytokine Modification and Stem Cell Mobilization for Acute Myocardial Infarction

  • Chapter
Stem Cells And Myocardial Regeneration

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

  • 694 Accesses

Abstract

Previous dogma held that an acute myocardial infarction (MI) resulted in absolute death of the involved myocardium and could only be modulated by reperfusion therapy. Recent data demonstrating the presence of a natural repair process stimulated by the release of chemokines in response to injury have challenged that belief. Unfortunately, this natural repair mechanism occurs at a rate that precludes any meaningful recovery of myocardial tissue and function. The feasibility of myocardial repair/regeneration has been demonstrated through delivery of either exogenously expanded stem cells or endogenously mobilized stem cells expanded by growth factors (i.e., granulocyte-colony-stimulating factor). Although data regarding the use of various growth factors in order to attenuate the extent of damage or facilitate repair of injured myocardium remain limited, the early experiences have suggested safety. From these data, one may envision a potential therapeutic strategy that augments the naturally occurring repair process early following a MI through mobilization of stem cells that will minimize damage and limit the dysfunction for a substantial proportion of patients.

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. Sell S. Heterogeneity and plasticity of hepatocyte lineage cells. Hepatology 2001;33:738–750.

    Article  PubMed  CAS  Google Scholar 

  2. Cohen IK, Diegelmann RF, Lindblad WJ, eds. Wound Healing: Biochemical and Clinical Aspects. Saunders, Philadelphia, 1992.

    Google Scholar 

  3. Veizovic T, Beech JS, Stroemer P, Watson WP, Hodges H. Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells. Stroke 2001;32:1012–1019.

    PubMed  CAS  Google Scholar 

  4. Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.

    PubMed  CAS  Google Scholar 

  5. 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 

  6. Jackson K, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 2001;107(11):1395–1402.

    Article  PubMed  CAS  Google Scholar 

  7. Sheiban I, Fragasso G, Lu C, Tonni S, Trevi GP, Chierchia SL. Influence of treatment delay on longterm left ventricular function in patients with acute myocardial infarction successfully treated with primary angioplasty. Am Heart J 2001;141:603–609.

    Article  PubMed  CAS  Google Scholar 

  8. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;327:397–402.

    Google Scholar 

  9. Assessment of the safety and efficacy of a new thrombolytic (ASSENT-2) investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomized trial. Lancet 1999;354:716–722.

    Article  Google Scholar 

  10. GUSTO IIb Angioplasty Substudy Investigators (Ellis SG, principal investigator). A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1997;336:1621–1628.

    Article  Google Scholar 

  11. Hochman JS, Buller CE, Sleeper LA, et al. Cardiogenic shock complicating acute myocardial infarction-etiologies, management and outcome: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock? J Am Coll Cardiol 2000;36:1063–1070.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004;44(8):1690–1699.

    Article  PubMed  Google Scholar 

  14. Kawada H, Fujita J, Kinjo K, et al. Non-hematopoetic mesenchymal stem cells can be mobilized and differentiated into cardiomyocytes after myocardial infarction. Blood 2004;104:12:3581–3587.

    Article  PubMed  CAS  Google Scholar 

  15. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002;297:2256–2259.

    Article  PubMed  CAS  Google Scholar 

  16. Quaini F, Urbanek K, Beltrami AP, et al. Chimerism of the transplanted heart. N Engl J Med 2002;346:5–15.

    Article  PubMed  Google Scholar 

  17. Bishop MR, Tarantolo SR, Jackson JD, et al. Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor. J Clin Oncol 1997;15:1601–1607.

    PubMed  CAS  Google Scholar 

  18. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001;7:430–436.

    Article  PubMed  CAS  Google Scholar 

  19. Schuster MD, Kocher AA, Seki T, et al. Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physicol Heart Circ Physiol 2004;287:H525–H532.

    Article  CAS  Google Scholar 

  20. Murry CE, Soonpaa MH, Reinecke H, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004;428.

    Google Scholar 

  21. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infracted heart, improving function and survival. PNAS 2001;98(18):10,344–10,349.

    Article  PubMed  CAS  Google Scholar 

  22. Rangappa S, Entwistle JWC, Wechsler AS, Kresh JY. Cardiomyocytes can induce human mesenchymal stem cells to express cardiac phenotype and genotype. Circulation 2002;106(19):II–235.

    Google Scholar 

  23. Fujita J, Suzuki Y, Ando K, et al. G-CSF improves post-infarction heart failure by mobilizing bone marrow stem cells, but GM-CSF increases the mortality by deteriorating heart function in mice. Circulation 2002;106(19):11–15.

    Google Scholar 

  24. Minatoguchi S, Takemura G, Chen XH, et al. Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment. Circulation 2004;109:2572–2580.

    Article  PubMed  CAS  Google Scholar 

  25. Sugano Y, Anzai T, Yoshikawa T, et al. Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction. Cardiovasc Res 2005;65:446–456.

    Article  CAS  Google Scholar 

  26. Harada M, Qin Y, Takano H, et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med 2005;11:305–311.

    Article  PubMed  CAS  Google Scholar 

  27. Orlic D, Arai AE, Sheikh FH, et al. Cytokine mobilized CD34+ cells do not benefit rhesus monkey following induced myocardial infarction. Blood 2002;100(11):28a.

    Google Scholar 

  28. Möhle R, Pförsich M, Fruehauf S, Witt B, Krämer A, Haas R. G-CSF post-chemotherapy mobilizes more CD34+ cells with use during steady-state hematopoiesis. Bone Marrow Transplant 1994;14:827–832.

    PubMed  Google Scholar 

  29. Meisenberg B, Brehm T, Schmeckel A, Miller W, McMillan R. A combination of low-dose cyclophosphamide and colony-stimulating factors is more cost-effective than granulocyte-colony-stimulating factors alone in mobilizing peripheral blood stem and progenitor cells. Transfusion 1998;38:209–215.

    Article  PubMed  CAS  Google Scholar 

  30. Copelan E, Ceselski S, Essone S, et al. Mobilization of peripheral-blood progenitor cells with highdose etoposide and granulocyte colony-stimulating factor in patients with breast cancer, non-Hodgkin’s lymphoma, and Hodgkin’s disease. J Clin Oncol 1997;15:759–765.

    PubMed  CAS  Google Scholar 

  31. Zsebo K, Wypych J, McNiece I, et al. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium. Cell 1990;63:195–201.

    Article  PubMed  CAS  Google Scholar 

  32. Anderson D, Lyman S, Baird A, et al. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 1990;63:235–243.

    Article  PubMed  CAS  Google Scholar 

  33. Martin F, Suggs S, Langley K, et al. Primary structure and functional expression of rat and human stem factor DNAs. Cell 1990;63:203–211.

    Article  PubMed  CAS  Google Scholar 

  34. Zsebo K, Willimas D, Geissler E, et al. Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990;63:213–224.

    Article  PubMed  CAS  Google Scholar 

  35. Glaspy JA, Shpall EJ, LeMaistre CF, et al. Peripheral blood progenitor cell mobilization using stem cell factor in combination with G-CSF in breast cancer patients. Blood 1997;90:2939–2951.

    PubMed  CAS  Google Scholar 

  36. Facon T, Harousseau J, Maloisel F, et al. Stem cell factor in combination with G-CSF after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. Blood 1999;94:1218–1225.

    PubMed  CAS  Google Scholar 

  37. Weaver A, Chang J, Wrigley E, et al. Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and G-CSF or chemotherapy plus G-CSF alone in patients with ovarian cancer. J Clin Oncol 1998;16:2601–2612.

    PubMed  CAS  Google Scholar 

  38. Stiff P, Gingrich R, Luger S, et al. A randomized phase 2 study of PBPC mobilization by stem cell factor and G-CSF in heavily pretreated patients with Hodgkin’s disease or non-Hodgkin’s lymphoma. Bone Marrow Transplant 2000;26:471–481.

    Article  PubMed  CAS  Google Scholar 

  39. Möhle R, Bautz F, Fafii S, et al. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic c ells and mediates transendothelial migration induced by stromal cellderived factor-1. Blood 1998;91:4523–4530.

    PubMed  Google Scholar 

  40. Aiuti A, Tavian M, Cipponi A, et al. Expression of CXCR4, the receptor for stromal cell-derived factor-1 on fetal and adult human lympho-hematopoietic progenitors. Eur J Immunol 1999;29:1823–1831.

    Article  PubMed  CAS  Google Scholar 

  41. Schols D, Esté J, Henson G, De Clercq E. Cibyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor Fusin/CXCR-4. Antiviral Res 1997;35:147–156.

    Article  PubMed  CAS  Google Scholar 

  42. Labrosse B, Brelot A, Heveker N, et al. Determinants for sensitivity of human immunodeficiency virus coreceptor CXCR4 to the bicyclam AMD3100. J Virol 1998;72:6381–6388.

    PubMed  CAS  Google Scholar 

  43. Egberink H, De Clercq E, Van Vliet A, et al. Bicyclams, selective antagonists of the Human chemokine receptor CXCR4, potently inhibit feline immunodeficiency virus replication. J Virol 1999;73:6346–6352.

    PubMed  CAS  Google Scholar 

  44. Viardot A, Kronenwett R, Deichmann M, Haas R. The human immunodeficiency virus (HIV)-type 1 coreceptor CXCR-4 (fusin) is preferentially expressed on the more immature CD34+ hematopoietic stem cells. Ann Hematol 1998;77:193–197.

    Article  PubMed  CAS  Google Scholar 

  45. Rosu-Myles M, Gallacher L, Murdoch B, et al. The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression. PNAS 2000;97:14,626–14,631.

    Article  PubMed  CAS  Google Scholar 

  46. Lataillade J, Clay D, Dupuy C, et al. Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood 2000;95:756–768.

    PubMed  CAS  Google Scholar 

  47. Hendrix C, Flexner C, MacFarland R, et al. Pharmacokinetics and safety of AMD 3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrobial agents and chemotherapy 2000;44:1667–1673.

    Article  PubMed  CAS  Google Scholar 

  48. Aiuti A, Webb I, Bleul C, Springer T, Gutierrez-Ramos JC. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997;185:111–120.

    Article  PubMed  CAS  Google Scholar 

  49. Lévesque J, Hendy J, Takamatsu Y, Simmons P, Bendall L. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSD or cyclophosphamide. J Clin Invest 2003;110:187–196.

    Article  CAS  Google Scholar 

  50. Lapidot T, Petit I. Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exper Hematol 2002;30:973–981.

    Article  CAS  Google Scholar 

  51. Liles W, Broxmeyer H, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003;102:2728–2730.

    Article  PubMed  CAS  Google Scholar 

  52. Liles W, Rodger E, Broxmeyer H, et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 2005;45:295–300.

    Article  PubMed  CAS  Google Scholar 

  53. Devine S, Flomenberg N, Vesole D, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin’s lymphoma. J Clin Oncol 2004;22:1095–1102.

    Article  PubMed  CAS  Google Scholar 

  54. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilized with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomized clinical trial. Lancet 2004;363:751–756.

    Article  PubMed  CAS  Google Scholar 

  55. O’Neill WW, Dixon SR, Grines CL. The year in interventional cardiology. J Am Coll Cardiol 2005;45(7):1117–1134.

    Article  PubMed  Google Scholar 

  56. Ellis SG, Penn M, Bolwell B, Brezina K, McConnell G. Randomized trial of G-CSF for patients with large acute myocardial infarction: preliminary results of phase 1 study. Am J Cardiol 2004;94(6):86E.

    Google Scholar 

  57. DeLezo JS, Pan M, Medina A, et al. Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: a randomized comparison of a simple versus complex strategy. Am Heart J 2004;148(5):857–864.

    Article  CAS  Google Scholar 

  58. Hill JM Syed MA Arai AE et al. Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease. J Am Coll Cardiol 2005;4691643–1648

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH

    Stephen G. Ellis MD

  2. Bone Marrow Transplant Program, Cleveland Clinic Foundation, Cleveland, OH

    Brian J. Bolwell MD

Authors
  1. Stephen G. Ellis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian J. Bolwell MD
    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

Ellis, S.G., Bolwell, B.J. (2007). Strategies for Cytokine Modification and Stem Cell Mobilization for Acute Myocardial Infarction. In: Penn, M.S. (eds) Stem Cells And Myocardial Regeneration. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-272-4_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-272-4_20

  • 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