Nature Medicine10, 494 - 501 (2004)
Published online: 25 April 2004; | doi:10.1038/nm1040
Bone marrow−derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation
Jens M Nygren1, Stefan Jovinge1, 2, Martin Breitbach3, Petter Säwén1, Wilhelm Röll4, Jürgen Hescheler5, Jalal Taneera1, Bernd K Fleischmann3
& Sten Eirik W Jacobsen1
1
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC B10, Klinikgatan 26, 221 84
Lund, Sweden.
2
Department of Cardiology, University Hospital MAS, Lund University, 205 02
Malmö, Sweden.
3
Institute of Physiology I, University of Bonn, Argelander-Str. 2a, 53115
Bonn, Germany.
4
Department of Cardiac Surgery, University of Bonn, Sigmund-Freud-Str. 25, 53105
Bonn, Germany.
5
Institute of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, 50931
Cologne, Germany.
Recent studies have suggested that bone marrow cells might possess a much broader differentiation potential than previously appreciated. In most cases, the reported efficiency of such plasticity has been rather low and, at least in some instances, is a consequence of cell fusion. After myocardial infarction, however, bone marrow cells have been suggested to extensively regenerate cardiomyocytes through transdifferentiation. Although bone marrow−derived cells are already being used in clinical trials, the exact identity, longevity and fate of these cells in infarcted myocardium have yet to be investigated in detail. Here we use various approaches to induce acute myocardial injury and deliver transgenically marked bone marrow cells to the injured myocardium. We show that unfractionated bone marrow cells and a purified population of hematopoietic stem and progenitor cells efficiently engraft within the infarcted myocardium. Engraftment was transient, however, and hematopoietic in nature. In contrast, bone marrow−derived cardiomyocytes were observed outside the infarcted myocardium at a low frequency and were derived exclusively through cell fusion.
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