Nygren, JM, Jovinge, S, Breitbach, M, Säwén, P, Röll, W, Hescheler, J et al.. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 10: 494-501

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.
Nature Medicine (Impact Factor: 27.36). 06/2004; 10(5):494-501. DOI: 10.1038/nm1040
Source: PubMed


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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Available from: Jalal Taneera, May 20, 2014
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    • "When they injected HSC into mice that underwent myocardial infarction, they did not observe any differentiation into cardiac myocytes. Injected cells simply differentiated into U n c o r r e c t e d P a p e r i n P r e s s the blood cells (Balsam et al., 2004), or fused with the cardiac cells (Nygren et al., 2004). Any beneficial effect could not be thus ascribed to the differentiation potential of bone marrow cells. "
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    • "In this paper, they demonstrated cardiac differentiation of transplanted HSCs; but this result was not confirmed by other groups [23] [24]. Instead, it emerged that HSCs generate cardiomyocytes with low frequency by fusion with resident cells [25] [26] but not by active cardiac differentiation. Emerging roles in cardiac disease therapies have been demonstrated for hematopoietic cytokines like GCSF, granulocyte macrophage colony-stimulating factor (GM-CSF), SCF, Flt-3 ligand, and erythropoietin (EPO). "
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    • "Evidence suggests that the microenvironment of injury could affect the migration, adherence and differentiation of transplanted stem cells [31-33]. Transplanted stem cells might transdifferentiate to tissue-specific cells, or fuse with the existing native cells, to improve the organ function by contributing their own genetic and cellular materials [33,34]. The development of ovarian follicles requires complex cell-cell interactions, as well as communication between somatic and germ cells. "
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