title: Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Nygren
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
authors.forename: Martin
authors.initials: M
authors.lastname: Breitbach
authors.forename: Petter
authors.initials: P
authors.lastname: Säwén
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Röll
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Jalal
authors.initials: J
authors.lastname: Taneera
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002465:Cell Movement; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007763:Lac Operon; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins