title: Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation.
abstract: BACKGROUND
  Hereditary disordered cardiac muscle could be replaced with intact cardiomyocytes derived from genetically intact bone marrow (BM)-derived stem cells.
  
  
  RESULTS
  Cardiomyopathic mice with targeted mutation of delta-sarcoglycan gene underwent intra-BM-BM transplantation (IBM-BMT) from transgenic mice expressing green fluorescence protein. The host BM and the peripheral blood were completely reconstituted by donor-derived hematopoietic cells by IBM-BMT. Treatment with granulocyte-colony stimulating factor (G-CSF) markedly increased donor-derived mesenchymal stem cells (MSC) in the BM and their mobilization into the peripheral blood after IBM-BMT. Treatment with isoproterenol (iso) for 7 days caused myocardial damage and left ventricular (LV) dysfunction in the cardiomyopathic mice. Co-treatment with iso and G-CSF increased donor BM cell recruitment to the heart and temporarily improved LV function in the cardiomyopathic mice with or without IBM-BMT. However, the cardiac muscle was not replaced with donor BM-derived cardiomyocytes in the cardiomyopathic mice with or without IBM-BMT, and this was associated with no improvement of LV function of mice aged 20 weeks.
  
  
  CONCLUSIONS
  These results suggest that G-CSF enhances engraftment of donor MSC in the BM and their mobilization into the peripheral circulation after IBM-BMT but MSC recruited to the heart do not differentiate into cardiomyocytes and do not repair the dystrophic heart.
authors.affiliation: The Department of Pediatrics, Kansai Medical University, Moriguchi, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Chiharu
authors.initials: C
authors.lastname: Enoki
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
authors.forename: Hiroji
authors.initials: H
authors.lastname: Imamura
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Taniuchi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016026:Bone Marrow Transplantation; D009202:Cardiomyopathies / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis; D017930:Genes, Reporter; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010210:Papillary Muscles / Q000187:drug effects / Q000473:pathology; D049031:Sarcoglycans / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D014916:Whole-Body Irradiation
chemical_list: D000318:Adrenergic beta-Agonists; D049031:Sarcoglycans; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D007545:Isoproterenol