Safety and Efficacy of Intramyocardial Implantation of Peripheral Blood Stem Cell for Cardiomyopathy
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Published:
Sep 20, 2011
Keywords:
Stem cells Cell transplantation Cardiomyopathy Heart failure Coronary artery bypass grafting
Main Article Content
Abstract
OBJECTIVE. To determine the safety and efficacy of intramyocardial autologous blood stem cell injection for cardiomyopathy.
MATERIALS AND METHODS. Between May 2005 and February 2010, 126 consecutive patients underwent intramyocardial cell injection. Fifty two were dilated cardiomyopathy (DCM) and 74 were ischemic cardiomyopathy (ICM). Mean age was 59.2 ± 12.4 years. The stem cells are isolated from the patient’s own blood and cultured. The final product is called angiogenic cell precursors (ACPs). The number of cells prior to injection was 46.1 ± 36.5 million cells. ACPs were injected into all areas of the left ventricle in DCM patients, and into the non-viable myocardium and hypokinetic segments in ICM patients. Combined coronary artery surgery and cell injection were performed in 33.8% of ICM cases.
RESULTS. There was no new ventricular arrhythmia. The 30-day mortality rate was 3.8% (2/52) and 4.1% (3/74) in DCM and ICM, respectively. New York Heart Association (NYHA) class improved from 3.0 ± 0.6 to 2.0 ± 0.9 at 485.8 ± 370.3 days (p < 0.001) in DCM and improved from 2.7 ± 0.6 to 1.9 ± 0.8 at 419.6 ± 345.5 days (p < 0.001) in ICM. Left ventricular ejection fraction (LVEF) increased from 23.3 ± 7.0% to 27.7 ± 11.3% at 409.7 ± 352.4 days (p = 0.03) in DCM and increased from 23.6 ± 7.7% to 31.5 ± 10.0% at 400.6 ± 350.1 days (p < 0.001) in ICM. Quality of life evaluated at 3 months has significantly improved for physical function, rolephysical, general health and vitality domains in DCM. For ICM, physical function, role-physical, general health and social function domains were also improved.
CONCLUSION. Intramyocardial ACPs injection is feasible and safe in both DCM and ICM. NYHA, quality of life and LVEF had significantly improved in both DCM and ICM.
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Ruengsakulrach P, Visudharom K, Chaothawee L, Belkin M. Safety and Efficacy of Intramyocardial Implantation of Peripheral Blood Stem Cell for Cardiomyopathy. BKK Med J [Internet]. 2011 Sep. 20 [cited 2024 Nov. 23];2(1):19. Available from: https://he02.tci-thaijo.org/index.php/bkkmedj/article/view/217713
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References
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11. Sun Z, Wu J, Fujii H, et al. Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes. Eur J Heart Fail 2008; 10:525-33.
12. Arom KV, Ruengsakulrach P, Jotisakulratana V. Intramyocardial angiogenic cell precursor injection for cardiomyopathy. Asian Cardiovasc Thorac Ann 2008; 16:143-8.
13. Ware J, Kosinski M, Keller SD. A 12-Item Short- Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34:220-33.
14. Kayisli UA, Luk J, Guzeloglu-Kayisli O, et al. Regulation of angiogenic activity of human endometrial endothelial cells in culture by ovarian steroids. J Clin Endocrinol Metab 2004;89:5794-802.
15. Arom K, Ruengsakulrach P, Jotisakulratana V. Efficacy of Intramyocardial Injection of Angiogenic Cell Precursors for Ischemic Cardiomyopathy: A Case Match Study. Innovations 2008;3:38-45.
16. Arom KV, Ruengsakulrach P, Belkin M, Tiensuwan M: Intramyocardial angiogenic cell precursors in nonischemic dilated cardiomyopathy. Asian Cardiovasc Thorac Ann 2009;17:382-8.
17. Sant’anna RT, Kalil RA, Pretto Neto AS, et al. Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action. Cell Transplant 2010;19:959-64.
18. Olgunturk R, Kula S, Sucak GT, et al. Peripheric stem cell transplantation in children with dilated cardiomyopathy: Preliminary report of first two cases. Pediatr Transplant 2010;14:257-60.
19. Seth S, Narang R, Bhargava B, et al. Percutaneous intrcoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial. J Am Coll Cardiol 2006;48:2350-51.
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21. Wang JA, Xie XJ, He H, et al. A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi 2006;34:107-10.
22. Chen Y, Gao EM, Gao CY, et al. Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi 2008;36:1087-91.
23. Roura S, Planas F, Prat-Vidal C, et al. Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation. Eur J Heart Fail 2007;9:995-02.
24. Werner L, Deutsch V, Barshack I, et al. Transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following experimental myocarditis. J Mol Cell Cardiol 2005;39:691-7.
25. Chu VF, Giaid A, Kuang JQ, et al. Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures. Ann Thorac Surg 1999;68:301-7; discussion 307-8.
26. Vrtovec B, Poglajen G, Sever M, et al. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail 2011;17:272-81.
27. Menasche P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 2008; 117:1189-200.
28. Pompilio G, Cannata A, Peccatori F, et al. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection. Ann Thorac Surg 2004;78:1808-12.
29. 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; 44:1690-9.
30. Meyer GP, Wollert KC, Lotz J, et al. 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;113:1287-94.
31. Gao LR, Wang ZG, Zhu ZM, et al. Effect of intracoronary transplantation of autologous bone marrow-derived mononuclear cells on outcomes of patients with refractory chronic heart failure secondary to ischemic cardiomyopathy. Am J Cardiol 2006;98:597-602.
32. Perin EC, Dohmann HF, Borojevic R, et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004;110(11 Suppl 1):II213-8.
33. Patel AN, Geffner L, Vina RF, et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg 2005;130:1631-8.
34. Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 2007;133:717-25.
35. Strauer BE, Brehm M, Zeus T, et al. 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 2005;46:1651-8.
36. Losordo DW, Schatz RA, White CJ, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 2007;115:3165-72.
37. Abdel-Latif A, Bolli R, Tleyjeh IM, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 2007; 167:989-97.
38. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004;363:751-6.
39. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;112 (9 Suppl):I150-6.
40. Zhang S, Wang D, Estrov Z, et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation 2004;110:3803-7.
41. Schenk S, Mal N, Finan A, et al. Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor. Stem Cells 2007;25:245-51.
42. Badorff C, Dimmeler S. Neovascularization and cardiac repair by bone marrow-derived stem cells. Handb Exp Pharmacol 2006;174:283-93.
43. Ott HC, Matthiesen TS, Brechtken J, et al. The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat Clin Pract Cardiovasc Med 2007;4 (Suppl 1):27-39.
44. Henning RJ, Burgos JD, Vasko M, et al. Human cord blood cells and myocardial infarction: effect of dose and route of administration on infarct size. Cell Transplant 2007;16:907-17.
45. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008;26:101-6.
46. Ebert SN, Taylor DG, Nguyen HL, et al. Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques. Stem Cells 2007;25:2936-44.
47. Doyle B, Kemp BJ, Chareonthaitawee P, et al. Dynamic tracking during intracoronary injection of 18F-FDGlabeled progenitor cell therapy for acute myocardial infarction. J Nucl Med 2007;48:1708-14.
48. Besler C, Doerries C, Giannotti G, et al. Pharmacological approaches to improve endothelial repair mechanisms. Expert Rev Cardiovasc Ther 2008;6:1071-82.
49. Kawamoto A, Murayama T, Kusano K, et al. Synergistic effect of bone marrow mobilization and vascular endothelial growth factor-2 gene therapy in myocardial ischemia. Circulation 2004;110:1398-405.
50. Cheng Z, Ou L, Zhou X, et al. Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 2008;16:571-9.
51. Shujia J, Haider HK, Idris NM, et al. Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. Cardiovasc Res 2008;77:525-33.
2. Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807-16.
3. Aronow WS. Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure. Cardiol Rev 2006;14:108-24.
4. Felker GM, Shaw LK, O’Connor CM. A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol 2002;39:210-8.
5. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a communitybased population. Jama 2004;292:344-50.
6. Meluzin J, Cerny J, Frelich M, et al. Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this Multicenter Study. J Am Coll Cardiol 1998;32:912-20.
7. Baker DW, Jones R, Hodges J, et al. Management of heart failure. III. The role of revascularization in the treatment of patients with moderate or severe left ventricular systolic dysfunction. Jama 1994;272:1528-34.
8. Allman KC, Shaw LJ, Hachamovitch R, et al. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol 2002;39:1151-8.
9. Ragosta M, Beller GA, Watson DD, et al. Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function. Circulation 1993;87:1630-41.
10. Porat Y, Porozov S, Belkin D, et al. Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages. Br J Haematol 2006; 135:703-14.
11. Sun Z, Wu J, Fujii H, et al. Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes. Eur J Heart Fail 2008; 10:525-33.
12. Arom KV, Ruengsakulrach P, Jotisakulratana V. Intramyocardial angiogenic cell precursor injection for cardiomyopathy. Asian Cardiovasc Thorac Ann 2008; 16:143-8.
13. Ware J, Kosinski M, Keller SD. A 12-Item Short- Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996; 34:220-33.
14. Kayisli UA, Luk J, Guzeloglu-Kayisli O, et al. Regulation of angiogenic activity of human endometrial endothelial cells in culture by ovarian steroids. J Clin Endocrinol Metab 2004;89:5794-802.
15. Arom K, Ruengsakulrach P, Jotisakulratana V. Efficacy of Intramyocardial Injection of Angiogenic Cell Precursors for Ischemic Cardiomyopathy: A Case Match Study. Innovations 2008;3:38-45.
16. Arom KV, Ruengsakulrach P, Belkin M, Tiensuwan M: Intramyocardial angiogenic cell precursors in nonischemic dilated cardiomyopathy. Asian Cardiovasc Thorac Ann 2009;17:382-8.
17. Sant’anna RT, Kalil RA, Pretto Neto AS, et al. Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action. Cell Transplant 2010;19:959-64.
18. Olgunturk R, Kula S, Sucak GT, et al. Peripheric stem cell transplantation in children with dilated cardiomyopathy: Preliminary report of first two cases. Pediatr Transplant 2010;14:257-60.
19. Seth S, Narang R, Bhargava B, et al. Percutaneous intrcoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial. J Am Coll Cardiol 2006;48:2350-51.
20. Fischer-Rasokat U, Assmus B, Seeger FH, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circ Heart Fail 2009;2:417-23.
21. Wang JA, Xie XJ, He H, et al. A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi 2006;34:107-10.
22. Chen Y, Gao EM, Gao CY, et al. Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi 2008;36:1087-91.
23. Roura S, Planas F, Prat-Vidal C, et al. Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation. Eur J Heart Fail 2007;9:995-02.
24. Werner L, Deutsch V, Barshack I, et al. Transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following experimental myocarditis. J Mol Cell Cardiol 2005;39:691-7.
25. Chu VF, Giaid A, Kuang JQ, et al. Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures. Ann Thorac Surg 1999;68:301-7; discussion 307-8.
26. Vrtovec B, Poglajen G, Sever M, et al. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail 2011;17:272-81.
27. Menasche P, Alfieri O, Janssens S, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation. Circulation 2008; 117:1189-200.
28. Pompilio G, Cannata A, Peccatori F, et al. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection. Ann Thorac Surg 2004;78:1808-12.
29. 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; 44:1690-9.
30. Meyer GP, Wollert KC, Lotz J, et al. 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;113:1287-94.
31. Gao LR, Wang ZG, Zhu ZM, et al. Effect of intracoronary transplantation of autologous bone marrow-derived mononuclear cells on outcomes of patients with refractory chronic heart failure secondary to ischemic cardiomyopathy. Am J Cardiol 2006;98:597-602.
32. Perin EC, Dohmann HF, Borojevic R, et al. Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004;110(11 Suppl 1):II213-8.
33. Patel AN, Geffner L, Vina RF, et al. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg 2005;130:1631-8.
34. Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 2007;133:717-25.
35. Strauer BE, Brehm M, Zeus T, et al. 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 2005;46:1651-8.
36. Losordo DW, Schatz RA, White CJ, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation 2007;115:3165-72.
37. Abdel-Latif A, Bolli R, Tleyjeh IM, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 2007; 167:989-97.
38. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004;363:751-6.
39. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;112 (9 Suppl):I150-6.
40. Zhang S, Wang D, Estrov Z, et al. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation 2004;110:3803-7.
41. Schenk S, Mal N, Finan A, et al. Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor. Stem Cells 2007;25:245-51.
42. Badorff C, Dimmeler S. Neovascularization and cardiac repair by bone marrow-derived stem cells. Handb Exp Pharmacol 2006;174:283-93.
43. Ott HC, Matthiesen TS, Brechtken J, et al. The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells. Nat Clin Pract Cardiovasc Med 2007;4 (Suppl 1):27-39.
44. Henning RJ, Burgos JD, Vasko M, et al. Human cord blood cells and myocardial infarction: effect of dose and route of administration on infarct size. Cell Transplant 2007;16:907-17.
45. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008;26:101-6.
46. Ebert SN, Taylor DG, Nguyen HL, et al. Noninvasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques. Stem Cells 2007;25:2936-44.
47. Doyle B, Kemp BJ, Chareonthaitawee P, et al. Dynamic tracking during intracoronary injection of 18F-FDGlabeled progenitor cell therapy for acute myocardial infarction. J Nucl Med 2007;48:1708-14.
48. Besler C, Doerries C, Giannotti G, et al. Pharmacological approaches to improve endothelial repair mechanisms. Expert Rev Cardiovasc Ther 2008;6:1071-82.
49. Kawamoto A, Murayama T, Kusano K, et al. Synergistic effect of bone marrow mobilization and vascular endothelial growth factor-2 gene therapy in myocardial ischemia. Circulation 2004;110:1398-405.
50. Cheng Z, Ou L, Zhou X, et al. Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 2008;16:571-9.
51. Shujia J, Haider HK, Idris NM, et al. Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. Cardiovasc Res 2008;77:525-33.