Objective: Bone marrow-derived circulating endothelial cells (EPCs) may migrate in ischemia zone, to stimulate resident progenitor cells to proliferation, differentiation and migration in a damage zone, and reduce an ischemia zone through formation of new vessels. Granulocyte colony stimulating factor (G- CSF) is well established to mobilize hematopoietic stem cells and might, thereby, also increase the pool of endogenously circulating EPCs. EPCs secrete pro-angiogenic factors. Therefore, we investigated the effects of G-CSF administration on mobilization and functional activities of bloodderived EPC in patients with chronic ischemic heart disease (CIHD).
Methods and Results: Ten patients with CIHD receive 300 μg per day subcutaneous G-CSF injection for 5 days. The number of EPCs, colony-forming capacity, tube formation and cytokine release were analyzed before and after G-CSF therapy. At day 5 of G-CSF treatment, the number of circulating CD34+CD45- and CD34+CD133+ and CD34+KDR+ cells significantly increased in patients with CIHD. Also, G-CSF therapy augmented the colony-forming capacity and tube formation by EPCs. Likewise, G-CSF treatment augmented cytokine production by circulating EPCs. Early EPCs and late EPCs produced a wide range of cytokines, which dependent the culture condition (gelatin-loaded or fibronectin-loaded surface of culture flask) and the days of cultivation (on day 8 or on day 16).
Conclusion: G-CSF treatment effectively mobilizes EPCs, which through paracrine factors production may influence at the resident progenitor cells in ischemic zone of heart to stimulate the repair of myocardium through neoangiogenesis.
Published on: Nov 29, 2016 Pages: 1-6