Granulocyte-colony stimulating factor directly enhances proliferation of human troponin I-positive cells derived from idiopathic dilated cardiomyopathy through specific receptors.
BACKGROUND
Our previous study showed that granulocyte-colony stimulating factor (G-CSF) enhanced bone-marrow-cell migration into the injured heart and that bone-marrow cells differentiated into cardiomyocytes. However, the number of bone-marrow-derived cardiomyocytes seems too small to have a direct, positive impact on pump function. Therefore, we hypothesized that G-CSF directly could affect the host myocardium through G-CSF receptors (G-CSFRs).


METHODS
In experiment 1, we cultured normal mouse heart cells with G-CSF at concentrations of 0, 1, 10, 50, and 100 ng/ml. In experiment 2, we cultured heart cells derived from a recipient with idiopathic cardiomyopathy (IDCM) after heart transplantation. We compared the total number of heart cells and Ki67- and troponin I (TnI)-positive cells with/without G-CSF at 50 ng/ml. We also performed immunochemical staining of the heart specimen from a recipient with IDCM using a rabbit polyclonal anti-G-CSFR antibody.


RESULTS
In experiment 1, mouse heart cells with G-CSF (50 ng/ml) proliferated maximally. In experiment 2, the total numbers of heart cells, Ki67-positive cells. TnI-positive cells, Ki67- and TnI-double-positive cells in the G-CSF group were greater than those in the non-G-CSF group at Days 14 and 28 (p <0.05). In the IDCM heart, G-CSFRs on cardiomyocytes were expressed heterogeneously and widely.


CONCLUSIONS
Granulocyte-colony stimulating factor directly enhanced the proliferation of TnI-positive cells derived from a recipient with IDCM through the G-CSFR.
Hamamoto
Masaki
M
Department of Regenerative Medicine and Tissue Engineering, Osaka, Japan.
Tomita
Shinji
S
Nakatani
Takeshi
T
Yutani
Chikao
C
Yamashiro
Seiji
S
Sueda
Taijiro
T
Yagihara
Toshikatsu
T
Kitamura
Soichiro
S
D000328:Adult; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis*; D019210:Troponin I / Q000032:analysis*
D019394:Ki-67 Antigen; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D019210:Troponin I; D016179:Granulocyte Colony-Stimulating Factor