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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 | Next Article 
Submitted December 18, 2006
Accepted April 20, 2007
Potential risks of bone marrow cell transplantation into infarcted hearts
Martin Breitbach, Toktam Bostani, Wilhelm Roell, Ying Xia, Oliver Dewald, Jens M Nygren, Jochen WU Fries, Klaus Tiemann, Heribert Bohlen, Juergen Hescheler, Armin Welz, Wilhelm Bloch, Sten Eirik W Jacobsen, and Bernd K Fleischmann*
Institute of Physiology I, University of Bonn, Bonn, Germany
Department of Cardiac Surgery, University of Bonn, Bonn, Germany
Institute of Neurophysiology, University of Cologne, Cologne, Germany
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
Department of Pathology, University of Cologne, Bonn, Germany
Department of Internal Medicine II, University of Bonn, Bonn, Germany
Axiogenesis AG, Cologne, Germany
Department of Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany
* Corresponding author; email: bernd.fleischmann{at}uni-bonn.de.
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, un-fractionated 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 (22/43, 51.2%) and un-fractionated BM cells (6/46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors (0/5, 0.0%), fibroblasts (0/5, 0.0%), vehicle only (0/30, 0.0%) or cytokine induced mobilization of BM cells (0/35, 0.0%). We conclude that the developmental fate of BM-derived cells is not restricted by the surrounding tissue post-myocardial infarction and that the MSC fraction underlies the extended bone formation in the infarcted myocardium. These findings seriously question the biological basis and clinical safety of utilizing whole BM and in particular MSCs to treat non-hematopoietic disorders.

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