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
  • Yosuke Hisashi
  • Shinji Tomita
  • Takeshi Nakatani
  • Shinya Fukuhara
  • Chikao Yutani
  • Soichiro Kitamura
Original Article

DOI: 10.1007/s11748-004-0138-4

Cite this article as:
Hisashi, Y., Tomita, S., Nakatani, T. et al. Jpn J Thorac Caridovasc Surg (2004) 52: 451. doi:10.1007/s11748-004-0138-4
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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) (1×106) via a tail vein (BMT). G-group (n=22) received G-CSF (50 µg/kg/day×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. Result: 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. Conclusion: 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.

Key words

granulocyte-colony stimulating factor bone marrow cells doxorubicin-induced cardiomyopathy migration phenotypic change 

Copyright information

© Japanese Association for Thoracic Surgery 2004

Authors and Affiliations

  • Yosuke Hisashi
    • 1
  • Shinji Tomita
    • 1
    • 2
  • Takeshi Nakatani
    • 3
  • Shinya Fukuhara
    • 1
  • Chikao Yutani
    • 4
  • Soichiro Kitamura
    • 2
  1. 1.Department of Regenerative Medicine and Tissue EngineeringNational Cardiovascular Research InstituteOsakaJapan
  2. 2.Department of Cardiovascular SurgeryNational Cardiovascular CenterOsakaJapan
  3. 3.Department of Organ TransplantationNational Cardiovascular CenterOsakaJapan
  4. 4.Department of PathologyNational Cardiovascular CenterOsakaJapan

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