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.