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(Circulation. 2003;107:1024.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
From Molecular Cardiology, Department of Internal Medicine IV (C.B., S.R., C.U., A.A., A.M.Z., S.D.), and the Institute for Cardiovascular Physiology (R.P.B., R.P., I.F., R.B), University of Frankfurt, Frankfurt, Germany.
Correspondence to Stefanie Dimmeler, Department of Molecular Cardiology, University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de
Background Further to promoting angiogenesis, cell therapy may be an approach for cardiac regeneration. Recent studies suggest that progenitor cells can transdifferentiate into other lineages. However, the transdifferentiation potential of endothelial progenitor cells (EPCs) is unknown.
Methods and Results EPCs were obtained from peripheral blood mononuclear cells of healthy adults or coronary artery disease (CAD) patients by cultivating with endothelial cell medium and growth factors. After 3 days, >95% of adherent cells were functionally and phenotypically EPCs. Diacetylated LDLlabeled EPCs were then cocultivated with rat cardiomyocytes for 6 days, resulting in significant increases of EPC cell length and size to a cardiomyocyte-like morphology. Biochemically, 9.94±1.39% and 5.04±1.09% of EPCs from healthy adults (n=15) or CAD patients (n=14, P<0.01 versus healthy adults), respectively, expressed
-sarcomeric actinin as measured by flow cytometry. Immunocytochemistry showed that human EPCs expressed
-sarcomeric actinin, cardiac troponin I (both with partial sarcomeric organization), atrial natriuretic peptide, and myocyte enhancer factor 2. Fluo 4 imaging demonstrated calcium transients synchronized with adjacent rat cardiomyocytes in transdifferentiated human EPCs. Single-cell microinjection of Lucifer yellow and calcein-AM labeling of cardiomyocytes demonstrated gap junctional communication between 51±7% of EPCs (16 hours after labeling, n=4) and cardiomyocytes. EPC transdifferentiation into cardiomyocytes was not observed with conditioned medium but in coculture with paraformaldehyde-fixed cardiomyocytes.
Conclusions EPCs from healthy volunteers and CAD patients can transdifferentiate in vitro into functionally active cardiomyocytes when cocultivated with rat cardiomyocytes. Cell-to-cell contact but not cellular fusion mediates EPC transdifferentiation. The therapeutic use of autologous EPCs may aid cardiomyocyte regeneration in patients with ischemic heart disease.
Key Words: myocytes physiology cells endothelium
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M. Xaymardan, J. Zheng, I. Duignan, A. Chin, J. M. Holm, V. L.T. Ballard, and J. M. Edelberg Senescent Impairment in Synergistic Cytokine Pathways That Provide Rapid Cardioprotection in the Rat Heart J. Exp. Med., March 15, 2004; 199(6): 797 - 804. [Abstract] [Full Text] [PDF] |
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M R Alison, R Poulsom, W R Otto, P Vig, M Brittan, N C Direkze, M Lovell, T C Fang, S L Preston, and N A Wright Recipes for adult stem cell plasticity: fusion cuisine or readymade? J. Clin. Pathol., February 1, 2004; 57(2): 113 - 120. [Abstract] [Full Text] [PDF] |
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D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis Cardiovasc Res, December 1, 2003; 60(3): 684 - 691. [Abstract] [Full Text] [PDF] |
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R. Gulati, D. Jevremovic, T. E. Peterson, S. Chatterjee, V. Shah, R. G. Vile, and R. D. Simari Diverse Origin and Function of Cells With Endothelial Phenotype Obtained From Adult Human Blood Circ. Res., November 28, 2003; 93(11): 1023 - 1025. [Abstract] [Full Text] [PDF] |
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M.B. Britten, N.D. Abolmaali, B. Assmus, R. Lehmann, J. Honold, J. Schmitt, T.J. Vogl, H. Martin, V. Schachinger, S. Dimmeler, et al. Infarct Remodeling After Intracoronary Progenitor Cell Treatment in Patients With Acute Myocardial Infarction (TOPCARE-AMI): Mechanistic Insights From Serial Contrast-Enhanced Magnetic Resonance Imaging Circulation, November 4, 2003; 108(18): 2212 - 2218. [Abstract] [Full Text] [PDF] |
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E. T.H. Yeh, S. Zhang, H. D. Wu, M. Korbling, J. T. Willerson, and Z. Estrov Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo Circulation, October 28, 2003; 108(17): 2070 - 2073. [Abstract] [Full Text] [PDF] |
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H. Oh, S. B. Bradfute, T. D. Gallardo, T. Nakamura, V. Gaussin, Y. Mishina, J. Pocius, L. H. Michael, R. R. Behringer, D. J. Garry, et al. Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction PNAS, October 14, 2003; 100(21): 12313 - 12318. [Abstract] [Full Text] [PDF] |
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M. Pesce, A. Orlandi, M. G. Iachininoto, S. Straino, A. R. Torella, V. Rizzuti, G. Pompilio, G. Bonanno, G. Scambia, and M. C. Capogrossi Myoendothelial Differentiation of Human Umbilical Cord Blood-Derived Stem Cells in Ischemic Limb Tissues Circ. Res., September 5, 2003; 93 (5): e51 - e62. [Abstract] [Full Text] [PDF] |
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E. N. Olson and M. D. Schneider Sizing up the heart: development redux in disease Genes & Dev., August 15, 2003; 17(16): 1937 - 1956. [Full Text] [PDF] |
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P. E. Szmitko, P. W.M. Fedak, R. D. Weisel, D. J. Stewart, M. J.B. Kutryk, and S. Verma Endothelial Progenitor Cells: New Hope for a Broken Heart Circulation, June 24, 2003; 107(24): 3093 - 3100. [Full Text] [PDF] |
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E. C. Perin, H. F.R. Dohmann, R. Borojevic, S. A. Silva, A. L.S. Sousa, C. T. Mesquita, M. I.D. Rossi, A. C. Carvalho, H. S. Dutra, H. J.F. Dohmann, et al. Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure Circulation, May 13, 2003; 107(18): 2294 - 2302. [Abstract] [Full Text] [PDF] |
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P. Anversa, J. Kajstura, B. Nadal-Ginard, and A. Leri Primitive Cells and Tissue Regeneration Circ. Res., April 4, 2003; 92(6): 579 - 582. [Full Text] [PDF] |
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