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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1362-1369.
Prepublished online as a Blood First Edition Paper on May 4, 2007; DOI 10.1182/blood-2006-12-063412.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Potential risks of bone marrow cell transplantation into infarcted hearts
Martin Breitbach1,
Toktam Bostani1,
Wilhelm Roell2,
Ying Xia3,
Oliver Dewald2,
Jens M. Nygren4,
Jochen W. U. Fries5,
Klaus Tiemann6,
Heribert Bohlen7,
Juergen Hescheler3,
Armin Welz2,
Wilhelm Bloch8,
Sten Eirik W. Jacobsen4, and
Bernd K. Fleischmann1
1 Institute of Physiology I and
2 Department of Cardiac Surgery, University of Bonn, Bonn, Germany;
3 Institute of Neurophysiology, University of Cologne, Cologne, Germany;
4 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden;
5 Department of Pathology, University of Cologne, Cologne, Germany;
6 Department of Internal Medicine II, University of Bonn, Bonn, Germany;
7 Axiogenesis AG, Cologne, Germany;
8 Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany
Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors (0 of 5, 0.0%), fibroblasts (0 of 5, 0.0%), vehicle only (0 of 30, 0.0%), or cytokine-induced mobilization of BM cells (0 of 35, 0.0%). We conclude that the developmental fate of BM-derived cells is not restricted by the surrounding tissue after myocardial infarction and that the MSC fraction underlies the extended bone formation in the infarcted myocardium. These findings seriously question the biologic basis and clinical safety of using whole BM and in particular MSCs to treat nonhematopoietic disorders.
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