Low-dose G-CSF improves fat graft retention by mobilizing endogenous stem cells and inducing angiogenesis, whereas high-dose G-CSF inhibits adipogenesis with prolonged inflammation and severe fibrosis

Background: Hematopoietic stem cells (HSCs) promote fat graft survival by modulating its revascularization. The authors hypothesize that mobilization of HSCs by G-CSF will improve fat graft survival. Hence, we evaluated the effect of different doses of G-CSF on fat grafting. Methods: Male 8 -week-old C57 mice received high-dose G-CSF (100 mu g/kg), low-dose G-CSF (10 mu g/kg), and PBS (control) intraperitoneally for 7 consecutive days right after autologous fat grafting. Grafted fat was harvested at 1, 4, and 12 weeks for examination. Results: The low-dose G-CSF, high-dose G-CSF, and control groups had retention rates of 73.6% +/- 3.1%, 51.6% +/- 4.4%, and 44.5% +/- 4.0%, respectively, at 12 weeks (low -dose G-CSF versus control and low -dose G-CSF versus high -dose G-CSF, both p < 0.05; no significant difference between high-dose G-CSF and control group). Both doses of G-CSF successfully mobilized HSCs into circulation and upregulated the level of blood-derived stem cells in fat grafts, contributing to improved angiogenesis. However, high dose G-CSF caused a prolonged macrophage infiltration and elevated level of inflammation (IL-6 and TNF-alpha), which led to severe fibrosis and impaired adipogenesis (downregulated expression of PPAR-gamma and CEBP-alpha). Conclusions: Low -dose G-CSF treatment successfully improved fat graft survival by mobilizing HSCs and inducing angiogenesis. However, high -dose G-CSF prolonged inflammation and caused severe fibrosis, leading to impaired adipogenesis and poor fat graft survival. (C) 2017 Published by Elsevier Inc.