Skip to main content

Angiogenesis Induced by Intramyocardial Implantation of Autologous Bone Marrow Mononuclear Cells for the Treatment of Ischemic Heart Disease

  • Chapter
  • 614 Accesses

Summary

Therapeutic angiogenesis has been successfully induced by various methods, and developed clinically as a new treatment for ischemic diseases. We have tried to induce therapeutic angiogenesis for the treatment of ischemic heart disease by the implantation of bone marrow mononuclear cells (BM-MNCs), because BM-MNCs consist of complex populations, including the endothelial progenitor and angiogenic cytokine-producing cells. Using the ischemic heart model in rats and dogs, we have demonstrated that the intramyocardial implantation of BM-MNCs is a feasible and safe method for inducing therapeutic angiogenesis and improving deteriorated cardiac function. Then, we performed the intramyocardial implantation of autologous BM-MNCs in eight patients with ischemic heart disease who underwent coronary arterial bypass graft (CABG) simultaneously. A specific increase in myocardial perfusion was seen in five patients, and two patients showed improved left ventricular wall motion, 1 and 12 months after treatment. No postoperative complications, new-onset malignant arrhythmias, mass formation or calcification, or any other abnormal signs related with this new therapy were detected in any of the patients by 3 years follow-up examination. Although further investigation on the safety and effect of cell-based therapy are required, our preliminary results indicated that the intramyocardial injection of BM-MNCs is a feasible and safe method of inducing therapeutic angiogenesis and improving cardiac function in patients with severe ischemic heart disease.

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

Buying options

Chapter
USD   29.95
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 PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, and Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964–967

    Article  PubMed  CAS  Google Scholar 

  • Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 106: 3009–3017

    Article  PubMed  Google Scholar 

  • Everaert H, Vanhove C, Franken PR. Assessment of perfusion, function, and myocardial metabolism after infarction with a combination of low-dose dobutamine tetrofosmin gated SPECT perfusion scintigraphy and BMIPP SPECT imaging. J Nucl Cardio 2000; 7: 29–36

    Article  CAS  Google Scholar 

  • Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, Waksman R, Weissman NJ, Cerqueira M, Leon MB, Epstein SE (2003) Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 2003; 41:1721–1724.

    Article  PubMed  Google Scholar 

  • Hamano K, Li TS, Kobayashi T, Hirata K, Yano M, Kohno M, Matsuzaki M (2002) Therapeutic angiogenesis induced by local autologous bone marrow cell implantation. Ann Thorac Surg 73:1210–1215

    Article  PubMed  Google Scholar 

  • Hamano K, Li T, Kobayashi T, Kobayashi S, Matsuzaki M, and Esato K (2000) Angiogenesis induced by the implantation of self-bone marrow cells: a new material for therapeutic angiogenesis. Cell Transplant 9:439–443

    PubMed  CAS  Google Scholar 

  • Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, and Esato K (2001) Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J 65:845–847

    Article  PubMed  CAS  Google Scholar 

  • Hayashi M, Li TS, Ito H, Mikamo A, Hamano K (In press) Comparison of intra-myocardial and intravenous routes of delivering bone marrow cells for the treatment of ischemic heart disease: an experimental study, Cell Transplant. In press

    Google Scholar 

  • Horvath KA, Cohn LH, Cooley DA, Crew JR, Frazier OH, Griffith BP, Kadipasaoglu K, Lansing A, Mannting F, March R, Mirhoseini MR, Smith C (1997) Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease. J Thorac Cardiovasc Surg 113: 645–653

    Article  PubMed  CAS  Google Scholar 

  • Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Masaki H, Mori Y, Iba O, Tateishi E, Kosaki A, Shintani S, Murohara T, Imaizumi T, Iwasaka T (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104:1046–1052

    PubMed  CAS  Google Scholar 

  • Kobayashi T, Hamano K, Li T, Katoh T, Kobayashi S, Matsuzaki M, and Esato K (2000). Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model. J Surg Res 89: 189–195, 2000

    Article  PubMed  CAS  Google Scholar 

  • Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardio-myocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7:430–6

    Article  PubMed  CAS  Google Scholar 

  • Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, and Rodgers GM. Wintrobe’s clinical hematology. 10th edition. Williams & Wilkins, A Waverly Company pp 145–168, 1998

    Google Scholar 

  • Li TS, Hamano K, Nishida M, Hayashi M, Ito H, Mikamo A, Matsuzaki M (2003) CD 117+ stem cells play a key role in therapeutic angiogenesis induced by bone marrow cell implantation. Am J Physiol Heart Circ Physiol 285:H931–937

    PubMed  CAS  Google Scholar 

  • Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Ashare AB, Lathi K, Isner JM (1998) Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804

    PubMed  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  PubMed  CAS  Google Scholar 

  • Patterson C (2003) The Ponzo effect: endothelial progenitor cells appear on the horizon. Circulation. 107:2995–2997

    Article  PubMed  Google Scholar 

  • Schumacher B, Pecher P, von Specht BU, Stegmann T (1998) Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease. Circulation 97:645–650

    PubMed  CAS  Google Scholar 

  • Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46

    Article  PubMed  Google Scholar 

  • Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, 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 

  • Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361:47–49

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Tokyo

About this chapter

Cite this chapter

Li, TS., Matsuzaki, M., Hamano, K. (2005). Angiogenesis Induced by Intramyocardial Implantation of Autologous Bone Marrow Mononuclear Cells for the Treatment of Ischemic Heart Disease. In: Mori, H., Matsuda, H. (eds) Cardiovascular Regeneration Therapies Using Tissue Engineering Approaches. Springer, Tokyo. https://doi.org/10.1007/4-431-27378-6_17

Download citation

  • DOI: https://doi.org/10.1007/4-431-27378-6_17

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-23925-3

  • Online ISBN: 978-4-431-27378-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics