Circulation. 2003;107:2294-2302
Published online before print April 21, 2003, doi: 10.1161/01.CIR.0000070596.30552.8B
Published online before print April 21, 2003, doi: 10.1161/01.CIR.0000070596.30552.8B
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(Circulation. 2003;107:2294.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure
From the Texas Heart Institute at St Luke’s Episcopal Hospital, Houston, Tex (E.C.P., G.V.S., Y.J.G., W.K.V., J.T.W.); Hospital Procardiaco, Rio de Janeiro, Brazil (H.F.R.D., S.A.S., A.L.S.S., C.T.M., H.J.F.D., L.B., R.V., F.O.D.R., R.E., J.A.R.A., E.T.M.); Federal University, Rio de Janeiro, Brazil (R.B., M.I.D.R., A.C.C., H.S.D.); and Brazilian Millennium Institute for Tissue Bioengineering (H.F.R.D., R.B., A.C.C.).
Correspondence to Emerson C. Perin, MD, 6624 Fannin, Suite 2220, Houston, TX 77030 (e-mail eperin{at}crescentb.net), and Hans F.R. Dohmann, MD, Rua General Polidoro, 192, CEP 22080-000–Botafogo, Rio de Janeiro, Brazil (e-mail hemodinamica@procardiaco.com.br).
Background— This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility.
Methods and Results— Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage 
6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (P=0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P=0.003) and a reduction in end-systolic volume (P=0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (P<0.0005) at 4 months after treatment.
Conclusions— Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow–derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.
Key Words: cells • heart failure • ischemia • revascularization • gene therapy
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F. G.P. Welt and D. W. Losordo Cell Therapy for Acute Myocardial Infarction: Curb Your Enthusiasm? Circulation, March 14, 2006; 113(10): 1272 - 1274. [Full Text] [PDF]
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I. Gruh, J. Beilner, U. Blomer, A. Schmiedl, I. Schmidt-Richter, M.-L. Kruse, A. Haverich, and U. Martin No Evidence of Transdifferentiation of Human Endothelial Progenitor Cells Into Cardiomyocytes After Coculture With Neonatal Rat Cardiomyocytes Circulation, March 14, 2006; 113(10): 1326 - 1334. [Abstract] [Full Text] [PDF]
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T. M. Kolettis Arrhythmogenesis after cell transplantation post-myocardial infarction. Four burning questions-And some answers Cardiovasc Res, February 1, 2006; 69(2): 299 - 301. [Full Text] [PDF]
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J. J. Minguell and A. Erices Mesenchymal Stem Cells and the Treatment of Cardiac Disease Experimental Biology and Medicine, January 1, 2006; 231(1): 39 - 49. [Abstract] [Full Text] [PDF]
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S. L.M.A. Beeres, D. E. Atsma, A. van der Laarse, D. A. Pijnappels, J. van Tuyn, W. E. Fibbe, A. A.F. de Vries, D. L. Ypey, E. E. van der Wall, and M. J. Schalij Human Adult Bone Marrow Mesenchymal Stem Cells Repair Experimental Conduction Block in Rat Cardiomyocyte Cultures J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1943 - 1952. [Abstract] [Full Text] [PDF]
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C. E. Murry, L. J. Field, and P. Menasche Cell-Based Cardiac Repair: Reflections at the 10-Year Point Circulation, November 15, 2005; 112(20): 3174 - 3183. [Full Text] [PDF]
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B. E. Strauer, M. Brehm, T. Zeus, T. Bartsch, C. Schannwell, C. Antke, R. V. Sorg, G. Kogler, P. Wernet, H.-W. Muller, 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., November 1, 2005; 46(9): 1651 - 1658. [Abstract] [Full Text] [PDF]
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R. Bolli, H. Jneid, and B. Dawn Bone Marrow Cell-Mediated Cardiac Regeneration: A Veritable Revolution J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1659 - 1661. [Full Text] [PDF]
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J. T. Willerson, E. T.H. Yeh, Y.-J. Geng, and E. C. Perin Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusions in Humans Circ. Res., October 14, 2005; 97(8): 735 - 736. [Full Text] [PDF]
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H. Yaoita, S. Takase, Y. Maruyama, Y. Sato, H. Satokawa, N. Hoshi, N. Ono, T. Igari, H. Ohto, and H. Yokoyama Scintigraphic Assessment of the Effects of Bone Marrow-Derived Mononuclear Cell Transplantation Combined with Off-Pump Coronary Artery Bypass Surgery in Patients with Ischemic Heart Disease J. Nucl. Med., October 1, 2005; 46(10): 1610 - 1617. [Abstract] [Full Text] [PDF]
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M. Valgimigli, G. M. Rigolin, C. Cittanti, P. Malagutti, S. Curello, G. Percoco, A. M. Bugli, M. D. Porta, L. Z. Bragotti, L. Ansani, et al. 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., September 2, 2005; 26(18): 1838 - 1845. [Abstract] [Full Text] [PDF]
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I. A. Memon, Y. Sawa, S. Miyagawa, S. Taketani, and H. Matsuda Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 646 - 653. [Abstract] [Full Text] [PDF]
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J. C Chachques, C. Salanson-Lajos, P. Lajos, A. Shafy, A. Alshamry, and A. Carpentier Cellular Cardiomyoplasty for Myocardial Regeneration Asian Cardiovasc Thorac Ann, September 1, 2005; 13(3): 287 - 296. [Abstract] [Full Text] [PDF]
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B.-O. Kim, H. Tian, K. Prasongsukarn, J. Wu, D. Angoulvant, S. Wnendt, A. Muhs, D. Spitkovsky, and R.-K. Li Cell Transplantation Improves Ventricular Function After a Myocardial Infarction: A Preclinical Study of Human Unrestricted Somatic Stem Cells in a Porcine Model Circulation, August 30, 2005; 112(9_suppl): I-96 - I-104. [Abstract] [Full Text] [PDF]
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H. F.R. Dohmann, E. C. Perin, C. M. Takiya, G. V. Silva, S. A. Silva, A. L.S. Sousa, C. T. Mesquita, M.-I. D. Rossi, B. M.O. Pascarelli, I. M. Assis, et al. Transendocardial Autologous Bone Marrow Mononuclear Cell Injection in Ischemic Heart Failure: Postmortem Anatomicopathologic and Immunohistochemical Findings Circulation, July 26, 2005; 112(4): 521 - 526. [Abstract] [Full Text] [PDF]
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