Abstract
Background
The Implantation of Autologous CD133+ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial
injections of autologous CD133+ stem cells during coronary artery bypass grafting (CABG) in patients with chronic
ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.
Methods
Bone marrow was harvested from iliac crests and stem cells were isolated using the
CliniMACS CD133+ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received
CABG, followed by CD133+ cellular injection in the revascularized hypokinetic myocardium.
Results
Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years
were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment
in CD133+ cells, with 92 ± 11% recovery after selection. Mean number of CD133+ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications
during the 18-month follow-up and all patients improved to NYHA class I. Six-month
echocardiography showed no significant improvement in left ventricular ejection fraction
(34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening
increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with
baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).
Conclusions
This work represents the first Canadian experience with CD133+ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate
the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients
are now being randomized to receive either CD133+ stem cell or placebo.
Résumé
Introduction
L’essai IMPACT-CABG (Implantation of Autologous CD133+ Stem Cells in Patients Undergoing Coronary Artery Bypass Grafting) examine la faisabilité, l’innocuité et l’efficacité des injections intramyocardiques
de cellules souches autologues CD133+ lors de pontage aortocoronarien (PAC) chez les patients ayant une cardiomyopathie
ischémique chronique. Nous rapportons les résultats des 5 premiers patients de l’essai
ouvert.
Méthodes
La moelle osseuse a été puisée des crêtes iliaques, et des cellules souches ont été
isolées en utilisant le CliniMACS CD133+ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Les patients ont subi un PAC,
suivi d’une injection de cellules CD133+ dans le myocarde hypokinétique revascularisé.
Résultats
Cinq (5) patients de sexe masculin appartenant à la classification III de la New York Heart Association (NYHA) âgés de 64 ± 10 ans ont été traités. Le processus de sélection cellulaire
immunomagnétique a permis un enrichissement moyen des cellules CD133+ de 100 ± 48 fois et un récupération après la sélection de 92 ± 11 %. Le nombre moyen
de cellules CD133+ injectées a été de 8,4 ± 1,2 millions. Il n’y a pas eu de complications liées au
protocole durant le suivi de 18 mois, et tous les patients se sont améliorés, c.-à-d.
qu’ils ont passé à la classification I de la NYHA. L’échocardiographie à 6 mois n’a
montré aucune amélioration significative de la fraction d’éjection ventriculaire gauche
(34 ± 2 % au début vs 38 ± 12 %: P = 0,50). Cependant, la résonance magnétique cardiaque a montré que l’épaisseur systolique
de la paroi avait augmenté de 15,0 ± 10,5 % à 29,0 ± 22,1 % (P = 0,01). De plus, l’épaisseur segmentaire moyenne de la paroi s’est aussi améliorée
comparativement au début (10,7 ± 2,7 % à 12,1 ± 4,8 %; P < 0,01).
Conclusions
Ce travail représente la première expérience canadienne sur les cellules souches CD133+ dans le traitement de la cardiomyopathie ischémique chronique. Ces résultats démontrent
l’innocuité et la faisabilité initiales de l’essai pilote IMPACT-CABG. D’autres patients
sont maintenant choisis de manière aléatoire pour recevoir soit les cellules souches
CD133+ ou le placebo.
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References
- Stem cells for the heart, are we there yet?.Cardiology. 2003; 100: 176-185
- Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study.J Thorac Cardiovasc Surg. 2005; 130: 1631-1638
- Molecular genetic advances in cardiovascular medicine: focus on the myocyte.Circulation. 2004; 109: 2832-2838
- Wanted! The best cell for cardiac regeneration.J Am Coll Cardiol. 2004; 44: 464-466
- Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells.Br J Haematol. 2001; 115: 186-194
- Haematopoietic stem cells and repair of the ischaemic heart.Clin Sci (Lond). 2005; 109: 483-492
- IMPACT-CABG: Implantation of CD133+ stem cells in patients undergoing coronary bypass surgery, presentation of the first treated patient.Case Reports in Transplantation. 2011; 2011 (Article ID 685394, 3 pages)
- The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.N Engl J Med. 2000; 343: 1445-1453
- An improved MR imaging technique for the visualization of myocardial infarction.Radiology. 2001; 218: 215-223
- Mesenchymal stem cells in the infarcted heart.Coron Artery Dis. 2005; 16: 93-97
- 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
- Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.N Engl J Med. 2006; 355: 1199-1209
- Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial.Eur Heart J. 2009; 30: 1313-1321
- Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety.Circulation. 2005; 112: I178-I183
- COMPARE-AMI trial: comparison of intracoronary injection of CD133+ bone marrow stem cells to placebo in patients after acute myocardial infarction and left ventricular dysfunction: study rationale and design.J Cardiovasc Transl Res. 2010; 3: 153-159
- Stem cell therapy for the broken heart: mini-organ transplantation.Transplantation Proc. 2009; 41: 3353-3357
- One-year safety analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction.Bone Marrow Res. 2011; 2011: 385124
- 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: 717-725
- CABG and bone marrow stem cell transplantation after myocardial infarction.Thorac Cardiovasc Surg. 2004; 52: 152-158
- Autologous bone-marrow stem-cell transplantation for myocardial regeneration.Lancet. 2003; 361: 45-46
- Autologous bone marrow cell transplantation combined with off-pump coronary artery bypass grafting in patients with ischemic cardiomyopathy.Can J Surg. 2008; 51: 269-275
- Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery.Ann Thorac Surg. 2008; 86: 1833-1840
- Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial.JAMA. 2009; 301: 1997-2004
- Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systemic review and meta-analysis.Circulation. 2012; 126: 551-568
- Impact of preoperative left ventricular function and time from infarction on the long-term benefits after intramyocardial CD133(+) bone marrow stem cell transplant.J Thorac Cardiovasc Surg. 2011; 142: 1530-1539.e3
- Cardiac cell therapy–mixed results from mixed cells.N Engl J Med. 2006; 355: 1274-1277
- Improved regional function after autologous bone marrow-derived stem cell transfer in patients with acute myocardial infarction: a randomized, double-blind strain rate imaging study.Eur Heart J. 2009; 30: 662-670
- The gold standard for noninvasive imaging in coronary heart disease: magnetic resonance imaging.Curr Opin Cardiol. 2009; 24: 567-579
Article info
Publication history
Published online: December 20, 2012
Accepted:
August 15,
2012
Received:
April 8,
2012
Footnotes
See page 446 for disclosure information.
Identification
Copyright
© 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Implantation of CD133+ Stem Cells in Patients Undergoing Coronary Bypass SurgeryCanadian Journal of CardiologyVol. 29Issue 11
- PreviewWe read with interest the article by Forcillo and colleagues1 on intramyocardial CD133+ autologous bone marrow stem cell application during coronary artery bypass grafting in patients with ischemic cardiomyopathy. This open-label pilot study of only 5 patients assessed safety and feasibility of the procedure. No increase in global ejection fraction was noted, but stress echocardiography and magnetic resonance imaging revealed improved regional contractility and morphology in the injected myocardium.
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