J Korean Med Assoc.  2006 Nov;49(11):1035-1045. 10.5124/jkma.2006.49.11.1035.

Stem Cell Therapy for Patients with Myocardial Infarction

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Korea. hyosoo@snu.ac.kr

Abstract

Several randomized placebo controlled clinical trials, which were based on the solid data from cell biologic, animal, and phase 1 clinical trials, have been published to demonstrate the efficacy of cell therapy to improve the contractility of myocardium in patients with myocardial infarction. Intracoronary infusion of the bone marrow mononuclear cells into infarct territory proved to be effective in improving coronary flow and contractility of the damaged myocardium in patients with AMI or OMI. Intracoronary infusion of the mobilized peripheral blood mononuclear cells with G-SF also proved to be effective in induction of angiomyogenesis in infarct territory of patients with AMI. Intramyocardial injection surgically or through catheter of autologous skeletal myoblast expanded ex vivo provided gain of LV contractility with possible side effect of arrhythmogenecity. From these trials we got the insight regarding the limitation and the solution to overcome it. In order to introduce cell therapy in the daily clinical practice, we have to find out the best protocol to ensure the reproducible and remarkable efficacy from active communication between basic and clinical researches. The limitation of efficacy in cell therapy may be overcome in two ways. One is to enhance the number and vitality/function of the cells for therapy. The other is to improve the homing/integration rate of transplanted cells to infarct territory after intracoronary infusion or intramyocardial injection.Stem cell therapy for angiomyogenesis in infarcted myocardium of patients proved to be effective. Future studies should be focused on to improve the limited efficacy and then to test the new protocols in large clinical trials.

Keyword

Stem cell; Myocardial infarction; Cell therapy; G-CSF; Bone marrow

MeSH Terms

Animals
Bone Marrow
Catheters
Cell- and Tissue-Based Therapy
Granulocyte Colony-Stimulating Factor
Humans
Myoblasts, Skeletal
Myocardial Infarction*
Myocardium
Stem Cells*
Granulocyte Colony-Stimulating Factor

Reference

1. Alison MR, Poulsom R, Forbes S, Wright NA. An introduction to stem cells. J Pathol. 2002. 07. 197:419–423.
Article
2. Asahara T, Murohara T, Sullivan A, Silver M, Zee R, Isner JM, et al. Isolation of Putative Progenitor Endothelial Cells for Angiogenesis. Science. 1997. 275:964–967.
Article
3. Asahara T, Kalka C, Isner JM. Stem cell therapy and gene transfer for regeneration. Gene Therapy. 2000. 7:451–457.
Article
4. Assmus B, Honold J, Schachinger V. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006. 355:1222–1232.
Article
5. Beltrami A, Barlucchi L, Torella D, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003. 114:763–776.
Article
6. Erbs S, Linke A, Adams V, Lenk K, Thiele H, Hambrecht R, et al. Transplantation of blood-erived progenitor cells after recanalization of chronic coronary artery occlusion: first randomized and placebo-ontrolled study. Circ Res. 2005. 97:756–762.
Article
7. Hill JM, Syed MA, Arai AE, Powell TM, Paul JD. Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease. J Am Coll Cardiol. 2005. 46:1643–1648.
Article
8. Hur J, Yoon CH, Choi JH, Kim HS, Oh BH, Park YB, et al. Characterization of Two Types of Endothelial Progenitor Cells and Their Different Cell Biologic Behaviors and Contribution to Neovasculogenesis. Arterioscl Thrombo Vasc Biol. 2004. 24:288–293.
Article
9. Ince H, Petzsch M, Kleine HD, Schmidt H, Rehders T, Korber T. Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte colony-stimulating factor (FIRSTLINE-AMI). Circulation. 2005. 112:3097–3106.
Article
10. Janssens S, Dubois C, Bogaert J. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet. 2006. 367:113–121.
Article
11. Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Park YB, et al. Intra-oronary Infusion of Peripheral Blood Stem Cells Mobilized with Granulocytes-Colony Stimulating Factor Induced not only Improvement of Left Ventricular Systolic Function but also Restenosis after Coronary Stenting in Patients with Myocardial Infarction. Lancet. 2004. 363:751–756.
Article
12. Kang HJ, Kim HS, Park YB. Stem cell therapy for myocardial infarction. Can Med Assoc J. 2004. 171:442.
Article
13. Kang HJ, Lee HY, Na SH, Chang SA, Park KW, Kim HS, et al. Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infraction versus old myocardial infarction: the MAGIC cell-3-DES randomized controlled trial. Circulation. 2006. 114:I145–I151.
14. Laugwitz KL, Moretti A, Lam J, Chien KR. Postnatal isl-1(+) cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2005. 433:647–653.
Article
15. Lunde K, Solheim S, Aakhus S. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006. 355:1199–1209.
Article
16. Makkar RR. Stem cell therapy for myocardial repair: is it arrhythmogenic? J Am Coll Cardiol. 2003. 42:2070–2072.
17. Menasche P. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003. 41:1078–1083.
Article
18. Meyer GP, Wollert KC, Lotz J. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (Bone marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006. 113:1287–1294.
Article
19. Murohara T, Ikeda H, Duan J, Shintani S, Sasaki K-I, Imaizumi T, et al. Transplanted cord blood derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest. 2000. 105:1527–1536.
Article
20. Oh H, Bradfute SB, Gallardo TD, Schneider MD. Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction. PNAS. 2003. 100:12313–12318.
Article
21. Pagani FD. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans: histological analysis of cell survival and differentiation. J Am Coll Cardiol. 2003. 41:879–888.
Article
22. Rosenzweig A. Cardiac cell therapy-mixed results from mixed cells. New Engl J Med. 2006. 355:1274–1277.
23. Schachinger V, Erbs S, Elsasser A, et al. Intracoronary bone marrow.derived progenitor cells in acute myocardial infarction. N Engl J Med. 2006. 355:1210–1221.
Article
24. Siminiak T. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J. 2004. 148:531–531.
Article
25. Smits PC. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol. 2003. 42:2063–2069.
Article
26. Steendijk P, Smits PC, Valgimigli M, van der Giessen WJ, Onderwater EE, Serruys PW. Intramyocardial injection of skeletal myoblasts: long-term follow-up with pressure-volume loops. Nature Clinical Practice Cardiovascular Medicine. 2006. 3:S94–S100.
Article
27. Valgimigli M, Rigolin GM, Cittanti C, Malagutti P, Curello S, Percoco G. 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. 2005. 26:1838–1845.
Article
28. Wollert KC, Meyer GP, Lotz J, Ringes-Lichtenberg S, Lippolt P, Drexler H, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004. 364:141–148.
Article
29. Yoon CY, Hur J, Park KW, Kim JH, Lee CS, Kim HS, et al. Synergistic Neovascularization by Mixed Transplantation of Early Endothelial Progenitor Cells and Late Outgrowth Endothelial Cells: The Role of Angiogenic Cytokines and Matrix Metalloproteinases. Circulation. 2005. 112:1618–1627.
Article
30. Zohlnhofer D, Ott I, Mehilli J, Schomig K, Michalk F, Ibrahim T. Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor in Patients With Acute Myocardial Infarction. JAMA. 2006. 295:1003–1010.
Article
Full Text Links
  • JKMA
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr