Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation

• Published in: Nature medicine Vol. 10; no. 5; pp. 494 - 501
• Main Authors: Jacobsen, Sten Eirik W, Nygren, Jens M, Jovinge, Stefan, Breitbach, Martin, Säwén, Petter, Röll, Wilhelm, Hescheler, Jürgen, Taneera, Jalal, Fleischmann, Bernd K
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.05.2004
• Subjects: Animals; Basic Medicine; Bone marrow; Cardiac; Cardiac and Cardiovascular Systems; Cell and Molecular Biology; Cell Differentiation; Cell Fusion; Cell Movement; Cell- och molekylärbiologi; Clinical Medicine; Graft Survival; Green Fluorescent Proteins; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Inbred C57BL; Kardiologi; Klinisk medicin; Lac Operon; Longevity; Luminescent Proteins; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myocardial Infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Plasticity; Recombinant Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Transgenic
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm1040

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.