This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (127)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Cardiovascular System  • Evidence-Based Medicine  • Transplantation  • Bone Marrow Transplantation  • Review  • Cardiovascular Disease/ Myocardial Infarction  • Congestive Heart Failure/ Cardiomyopathy  • Alert me on articles by topic  Social Bookmarking   What's this?

A Systematic Review and Meta-analysis

Ahmed Abdel-Latif, MD; Roberto Bolli, MD; Imad M. Tleyjeh, MD, MSc; Victor M. Montori, MD, MSc; Emerson C. Perin, MD; Carlton A. Hornung, PhD, MPH; Ewa K. Zuba-Surma, PhD; Mouaz Al-Mallah, MD; Buddhadeb Dawn, MD

Arch Intern Med. 2007;167(10):989-997.

Background  The results from small clinical studies suggest that therapy with adult bone marrow (BM)–derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear.

Methods  We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes.

Results  Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (–5.49%; 95% CI, –9.10% to –1.88%; P = .003); and reduced left ventricular end-systolic volume (–4.80 mL; 95% CI, –8.20 to –1.41 mL; P = .006).

Conclusions  The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

Author Affiliations: Division of Cardiology and the Institute of Molecular Cardiology (Drs Abdel-Latif, Bolli, Zuba-Surma, and Dawn) and Department of Epidemiology and Population Health, School of Public Health and Information Sciences (Dr Hornung), University of Louisville, Louisville, Ky; Knowledge and Encounter Research Unit, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minn (Drs Tleyjeh and Montori); King Fahd Medical City, Riyadh, Saudi Arabia (Dr Tleyjeh); Department of Cardiology, University of Texas, Houston (Dr Perin); and Division of Cardiovascular Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (Dr Al-Mallah).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Cell-based therapy for ischemic heart disease: a clinical update.
Herrmann et al.
Ann. Thorac. Surg. 2009;88:1714-1722.
ABSTRACT | FULL TEXT  

Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy
Leong-Poi
Cardiovasc Res 2009;84:190-200.
ABSTRACT | FULL TEXT  

Magnetic resonance imaging of human endothelial progenitors reveals opposite effects on vascular and muscle regeneration into ischaemic tissues
Gianella et al.
Cardiovasc Res 2009;0:cvp325v2-cvp325.
ABSTRACT | FULL TEXT  

The Hedgehog Transcription Factor Gli3 Modulates Angiogenesis
Renault et al.
Circ. Res. 2009;105:818-826.
ABSTRACT | FULL TEXT  

Myocardial Salvage Through Coronary Collateral Growth by Granulocyte Colony-Stimulating Factor in Chronic Coronary Artery Disease: A Controlled Randomized Trial
Meier et al.
Circulation 2009;120:1355-1363.
ABSTRACT | FULL TEXT  

Randomized controlled trial on the cardioprotective effect of bone marrow cells in patients undergoing coronary bypass graft surgery
Lai et al.
Eur Heart J 2009;30:2354-2359.
ABSTRACT | FULL TEXT  

Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial
Schachinger et al.
Eur J Heart Fail 2009;11:973-979.
ABSTRACT | FULL TEXT  

Cardiac Cell Repair Therapy: A Clinical Perspective
Gersh et al.
Mayo Clin Proc. 2009;84:876-892.
ABSTRACT | FULL TEXT  

Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial
Meyer et al.
Eur Heart J 2009;0:ehp374v1-ehp374.
ABSTRACT | FULL TEXT  

Engraftment, Differentiation, and Functional Benefits of Autologous Cardiosphere-Derived Cells in Porcine Ischemic Cardiomyopathy
Johnston et al.
Circulation 2009;120:1075-1083.
ABSTRACT | FULL TEXT  

Identification of a coronary vascular progenitor cell in the human heart
Bearzi et al.
Proc. Natl. Acad. Sci. USA 2009;106:15885-15890.
ABSTRACT | FULL TEXT  

Cardiac Progenitor Cells and Biotinylated Insulin-Like Growth Factor-1 Nanofibers Improve Endogenous and Exogenous Myocardial Regeneration After Infarction
Padin-Iruegas et al.
Circulation 2009;120:876-887.
ABSTRACT | FULL TEXT  

Endogenous stem cells in patients undergoing coronary artery bypass graft surgery
Dotsenko and Jahangiri
Eur. J. Cardiothorac. Surg. 2009;36:563-571.
ABSTRACT | FULL TEXT  

Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart.
Abarbanell et al.
Ann. Thorac. Surg. 2009;88:1036-1043.
ABSTRACT | FULL TEXT  

Magnetic Resonance Labeling of Stem Cells: Is Positive Tracking a Plus or a Minus?
Kraitchman and Caravan
J Am Coll Cardiol Img 2009;2:1123-1125.
FULL TEXT  

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
Fischer-Rasokat et al.
Circ Heart Fail 2009;2:417-423.
ABSTRACT | FULL TEXT  

Route of delivery and baseline left ventricular ejection fraction, key factors of bone-marrow-derived cell therapy for ischaemic heart disease
Brunskill et al.
Eur J Heart Fail 2009;11:887-896.
ABSTRACT | FULL TEXT  

Molecular imaging of endothelial progenitor cell engraftment using contrast-enhanced ultrasound and targeted microbubbles
Kuliszewski et al.
Cardiovasc Res 2009;83:653-662.
ABSTRACT | FULL TEXT  

Magnetic Tagging Increases Delivery of Circulating Progenitors in Vascular Injury
Kyrtatos et al.
J Am Coll Cardiol Intv 2009;2:794-802.
ABSTRACT | FULL TEXT  

Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease
Boudoulas and Hatzopoulos
DMM 2009;2:344-358.
ABSTRACT | FULL TEXT  

Add Some Fat to Vascular Progenitor Cell Therapy
Saif et al.
Circ. Res. 2009;104:1330-1332.
FULL TEXT  

Robust Functional Vascular Network Formation In Vivo by Cooperation of Adipose Progenitor and Endothelial Cells
Traktuev et al.
Circ. Res. 2009;104:1410-1420.
ABSTRACT | FULL TEXT  

The BALANCE Study: clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction.
Yousef et al.
J Am Coll Cardiol 2009;53:2262-2269.
ABSTRACT | FULL TEXT  

Long-term outcome of stem cell therapy for acute myocardial infarction: right results, wrong reasons.
Forrester et al.
J Am Coll Cardiol 2009;53:2270-2272.
FULL TEXT  

A heart full of stem cells: the spectrum of myocardial progenitor cells in the postnatal heart
Stamm et al.
Ther Adv Cardiovasc Dis 2009;3:215-229.
ABSTRACT  

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
Tendera et al.
Eur Heart J 2009;30:1313-1321.
ABSTRACT | FULL TEXT  

Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor-{alpha} via the p38 mitogen-activated protein kinase pathway
Zhang et al.
FASEB J. 2009;23:1358-1365.
ABSTRACT | FULL TEXT  

An acellular matrix-bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model
Suuronen et al.
FASEB J. 2009;23:1447-1458.
ABSTRACT | FULL TEXT  

Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells
Zhang et al.
Am. J. Physiol. Heart Circ. Physiol. 2009;296:H1675-H1682.
ABSTRACT | FULL TEXT  

Stem Cell Therapy Is Proarrhythmic
Macia and Boyden
Circulation 2009;119:1814-1823.
FULL TEXT  

Stem Cells Are Not Proarrhythmic: Letting the Genie out of the Bottle
Ly and Nattel
Circulation 2009;119:1824-1831.
FULL TEXT  

Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes
Lee et al.
Am. J. Physiol. Heart Circ. Physiol. 2009;296:H927-H936.
ABSTRACT | FULL TEXT  

Incidence, determinants, and prognostic value of reverse left ventricular remodelling after primary percutaneous coronary intervention: results of the Acute Myocardial Infarction Contrast Imaging (AMICI) multicenter study
Funaro et al.
Eur Heart J 2009;30:566-575.
ABSTRACT | FULL TEXT  

Cell therapy generates a favourable chemokine gradient for stem cell recruitment into the infarcted heart in rabbits
Lee et al.
Eur J Heart Fail 2009;11:238-245.
ABSTRACT | FULL TEXT  

Where Have All the Stem Cells Gone?
Bagi and Kaley
Circ. Res. 2009;104:280-281.
FULL TEXT  

Dual Angiogenic and Neurotrophic Effects of Bone Marrow-Derived Endothelial Progenitor Cells on Diabetic Neuropathy
Jeong et al.
Circulation 2009;119:699-708.
ABSTRACT | FULL TEXT  

Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs
Vela et al.
J. Histochem. Cytochem. 2009;57:167-176.
ABSTRACT | FULL TEXT  

Pravastatin Improves Function in Hibernating Myocardium by Mobilizing CD133+ and cKit+ Bone Marrow Progenitor Cells and Promoting Myocytes to Reenter the Growth Phase of the Cardiac Cell Cycle
Suzuki et al.
Circ. Res. 2009;104:255-264.
ABSTRACT | FULL TEXT  

Promise of Blood- and Bone Marrow-Derived Stem Cell Transplantation for Functional Cardiac Repair Putting It in Perspective With Existing Therapy.
Reffelmann et al.
J Am Coll Cardiol 2009;53:305-308.
ABSTRACT | FULL TEXT  

Cellular Cardiomyoplasty: What Have We Learned?
Kao et al.
Asian Cardiovasc. Thorac. Ann. 2009;17:89-101.
ABSTRACT | FULL TEXT  

New Paradigms of Myocardial Regeneration Post-Infarction: Tissue Preservation, Cell Environment, and Pluripotent Cell Sources
Forrester et al.
J Am Coll Cardiol Intv 2009;2:1-8.
ABSTRACT | FULL TEXT  

Insights into mechanisms behind arteriogenesis: what does the future hold?
van Oostrom et al.
J. Leukoc. Biol. 2008;84:1379-1391.
ABSTRACT | FULL TEXT  

"B2 or not B2?": Kinin Receptors and Endothelial Progenitor Cell Dysfunction
Ward et al.
Circ. Res. 2008;103:1202-1203.
FULL TEXT  

From Genes to Regenerative Medicine: Approaches in Development
Ruel et al.
Circ. Res. 2008;103:1050-1052.
FULL TEXT  

Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells: Development and Demonstration by Ex Vivo Radionuclide Cell Labeling and In Vivo Tracking With Positron-Emission Tomography
Zhang et al.
Circ Cardiovasc Imaging 2008;1:197-204.
ABSTRACT | FULL TEXT  

Clinical trials in stem cell transplantation: guidelines for scientific and ethical review
Lo et al.
Clin Trials 2008;5:517-522.
ABSTRACT  

Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium
Schachinger et al.
Circulation 2008;118:1425-1432.
ABSTRACT | FULL TEXT  

A Factor Underlying Late-Phase Arrhythmogenicity After Cell Therapy to the Heart: Global Downregulation of Connexin43 in the Host Myocardium After Skeletal Myoblast Transplantation
Coppen et al.
Circulation 2008;118:S138-S144.
ABSTRACT | FULL TEXT  

Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review
Martin-Rendon et al.
Eur Heart J 2008;29:1807-1818.
ABSTRACT | FULL TEXT  

Erythropoietin and mesenchymal stromal cells in angiogenesis and myocardial regeneration: one plus one equals three?
Ward and Stewart
Cardiovasc Res 2008;79:357-359.
FULL TEXT  

Review: Endothelial progenitor cells: markers of vascular reparative capacity
Povsic and Goldschmidt-Clermont
Ther Adv Cardiovasc Dis 2008;2:199-213.
ABSTRACT  

An Inconvenient Truth: Recognizing Individual Differences in Arteriogenesis
Rehman
Circ. Res. 2008;102:1146-1147.
FULL TEXT  

The Stem Cell Movement
Smart and Riley
Circ. Res. 2008;102:1155-1168.
ABSTRACT | FULL TEXT  

The Management of Heart Failure: The Past, the Present, and the Future
Braunwald
Circ Heart Fail 2008;1:58-62.
FULL TEXT  

Noncanonical Wnt11 Signaling Is Sufficient to Induce Cardiomyogenic Differentiation in Unfractionated Bone Marrow Mononuclear Cells
Flaherty et al.
Circulation 2008;117:2241-2252.
ABSTRACT | FULL TEXT  

Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor for Myocardial Recovery After Acute Myocardial Infarction: A Meta-Analysis
Zohlnhofer et al.
J Am Coll Cardiol 2008;51:1429-1437.
ABSTRACT | FULL TEXT  

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation
Menasche et al.
Circulation 2008;117:1189-1200.
ABSTRACT | FULL TEXT  

Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases
Burt et al.
JAMA 2008;299:925-936.
ABSTRACT | FULL TEXT