G-CSF promotes bone marrow cells to migrate into infarcted mice heart, and differentiate into cardiomyocytes.
A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 10(6) cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 microg/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3+/-71.9/mm2) were located at the infarcted border area significantly more than those in group 2 (43.6+/-23.7/mm2) (p < 0.0001). BMD-GFP cells were positive for troponin I (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0+/-7.0/mm2) were significantly more than those in group 2 (4.8+/-6.1/mm2) (p = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.
Fukuhara
Shinya
S
Department of Regenerative Medicine & Tissue Engineering, National Cardiovascular Center, Osaka, Japan. shinyafukuhara@hotmail.com
Tomita
Shinji
S
Nakatani
Takeshi
T
Ohtsu
Yoshinori
Y
Ishida
Michiko
M
Yutani
Chikao
C
Kitamura
Soichiro
S
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D049452:Green Fluorescent Proteins; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015996:Survival Rate; D018183:Transplantation Chimera; D016896:Treatment Outcome; D019210:Troponin I / Q000378:metabolism
D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011993:Recombinant Fusion Proteins; D019210:Troponin I; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D018995:Myosin Heavy Chains