title: Granulocyte-colony stimulating factor enhanced the recruitment of bone marrow cells into the heart: time course evaluation of phenotypic differentiation in the doxorubicin-induced cardiomyopathic model.
abstract: OBJECTIVE
  We traced and evaluated bone marrow-derived cells after granulocyte-colony stimulating factor (G-CSF) treatment in the doxorubicin-induced cardiomyopathic heart in the time course.
  
  
  METHODS
  C57BL/6 male mice received doxorubicin (15 mg/kg, i.p.). At 1 week after administration of doxorubicin, the mice were irradiated (900 cGy) followed by transplantation of bone marrow cells (BMT) derived from transgenic mice expressing green fluorescent protein (GFP) (1 x 10(6)) via a tail vein (BMT). G-group (n = 22) received G-CSF (50 microg/kg/day x 8 days, s.c.) after BMT, while C-group (n = 17) received saline. At 4 and 7 weeks after BMT, heart sections were fixed to evaluate bone marrow-derived GFP cells (BMD-GFP) with immunostaining for Troponin I (TnI), atrial-natriuretic peptide (ANP), connexin 43, von Willebrand factor, and Ki67.
  
  
  RESULTS
  There were migrated BMD-GFP in the whole heart of all animals. In the time course, migrated BMD-GFP increased in G-group. At 7 weeks the number of migrated BMD-GFP in G-group (56.2 +/- 15.6/HPF) was larger than that in C-group (18.9 +/- 10.7/HPF) (p < 0.05). TnI- and connexin 43-positive BMD-GFP were spindle-shaped. Von Willebrand factor-positive BMD-GFP showed thinner-shape. ANP- and Ki67-positive BMD-GFP showed oval-shape. The numbers of these positive cells derived from BMD-GFP, not different between the 2 groups, did not change from 4 to 7 weeks.
  
  
  CONCLUSIONS
  The migration of BMD-GFP into the heart increased from 4 to 7 weeks after BMT by G-CSF. However, cardiomyocytes and endothelial cells originating from BMD-GFP were very few and neither increased nor changed in their shapes and numbers in the short term.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hisashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Tomita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Shinya
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Chikao
authors.initials: C
authors.lastname: Yutani
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D016026:Bone Marrow Transplantation; D009202:Cardiomyopathies; D002465:Cell Movement / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D018709:Statistics, Nonparametric
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin