title: Bone marrow-derived cardiomyocytes are present in adult human heart: A study of gender-mismatched bone marrow transplantation patients.
abstract: BACKGROUND
  Recent studies have identified cardiomyocytes of extracardiac origin in transplanted human hearts, but the exact origin of these myocyte progenitors is currently unknown.
  
  
  RESULTS
  Hearts of female subjects (n=4) who had undergone sex-mismatched bone marrow transplantation (BMT) were recovered at autopsy and analyzed for the presence of Y chromosome-positive cardiomyocytes. Four female gender-matched BMT subjects served as controls. Fluorescence in situ hybridization (FISH) for the Y chromosome was performed on paraffin-embedded sections to identify cells of bone marrow origin with concomitant immunofluorescent labeling for alpha-sarcomeric actin to identify cardiomyocytes. A total of 160 000 cardiomyocyte nuclei were analyzed approximating 20 000 nuclei per patient. The mean percentage of Y chromosome-positive cardiomyocytes in patients with sex-mismatched BMT was 0.23+/-0.06%. Not a single Y chromosome-positive cardiomyocyte was identified in any of the control patients. Immunofluorescent costaining for laminin and chromosomal ploidy analysis with FISH showed no evidence of either pseudonuclei or cell fusion in any of the chimeric cardiac myocytes identified.
  
  
  CONCLUSIONS
  These data establish for the first time human bone marrow as a source of extracardiac progenitor cells capable of de novo cardiomyocyte formation.
authors.affiliation: Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, Minn 55905, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Deb
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Skelding
authors.forename: Dylan
authors.initials: D
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Simper
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
mesh_terms: D000199:Actins / Q000032:analysis / Q000276:immunology; D000328:Adult; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D041322:Chromosomes, Human, Y; D005260:Female; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology*; D014019:Tissue Donors; D018183:Transplantation Chimera
chemical_list: D000199:Actins