G-CSF treatment increases side population cell infiltration after myocardial infarction in mice.
Granulocyte-colony stimulating factor (G-CSF) has been reported to mobilize bone marrow multi-potent stem cells, which differentiate into cardiac myocytes after myocardial infarction (MI). However, there have not been any reports regarding the effect of G-CSF on stem cell infiltration in the MI site. Hearts of mice that had undergone coronary occlusion were isolated and digested with collagenase. Infiltrating cells in the heart were collected using Percoll density gradients. The infiltrating cells were sorted for side population (SP) cells using Hoechst 33342 dye. Hundreds of infiltrating SP cells were found in the heart from 1 to 14 d after MI. There were only a few SP cells in hearts without infarction. Infiltrating SP cells were increased in the 4-d G-CSF treated group compared with the vehicle group (1106 +/- 106 vs. 323 +/- 26/heart, P < 0.05). The infiltration of inflammatory cells was not influenced by the G-CSF treatment. In a separate series of experiments, we confirmed that the infiltrating SP cells were derived from bone marrow. That is, SP cells in the infarcted hearts of mice, which had been transplanted with bone marrow from ROSA 26 (beta-galactosidase transgenic) mice, were positive for beta-galactosidase. In the immunohistochemical examination, Sca-1(+)/CD45(-) cells were existed in the infarcted site after MI. Therefore, SP cells may infiltrate into infarcted heart. G-CSF augmented this kind of stem cell infiltration without increasing inflammatory cells. These results suggest that G-CSF may enhance myocardial regeneration without aggravated inflammation in the infarcted heart.
Adachi
Yuichiro
Y
Pharmaceutical Research Department I, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Imagawa
Jun-Ichi
J
Suzuki
Yoshiyuki
Y
Yogo
Kenji
K
Fukazawa
Masanori
M
Kuromaru
Osamu
O
Saito
Yoshihiko
Y
D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology*
D016179:Granulocyte Colony-Stimulating Factor