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
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
复制标题
低剂量 G-CSF 通过动员内源干细胞和诱导血管生成来改善脂肪移植保留，而高剂量 G-CSF 会抑制脂肪生成，导致长期炎症和严重纤维化
DOI：
10.1016/j.bbrc.2017.07.147
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发表时间：
2017-09-23
影响因子：
3.1
通讯作者：
Lu, Feng
中科院分区：
文献类型：
--
作者：
Cai, Junrong;Li, Bin;Lu, Feng
背景：造血干细胞（hsc）通过调节脂肪移植物的血运重建来促进其存活。作者推测G-CSF对hsc的动员可以提高脂肪移植物的存活率。因此，我们评估了不同剂量的G-CSF对脂肪移植的影响。方法：雄性8周龄C57小鼠自体脂肪移植后，连续7天腹腔注射高剂量g - csf （100 μ g/kg）、低剂量g - csf （10 μ g/kg）和PBS（对照）。在第1周、第4周和第12周采集移植脂肪进行检查。结果：低剂量G-CSF组、高剂量G-CSF组和对照组在12周时的保留率分别为73.6% +/- 3.1%、51.6% +/- 4.4%和44.5% +/- 4.0%（低剂量G-CSF相对于对照组、低剂量G-CSF相对于高剂量G-CSF， p均< 0.05；高剂量G-CSF与对照组无显著差异）。两种剂量的G-CSF都成功地将hsc动员到循环中，并上调了脂肪移植物中血源性干细胞的水平，有助于改善血管生成。然而，高剂量G-CSF导致巨噬细胞浸润时间延长，炎症（IL-6和tnf - α）水平升高，导致严重纤维化和脂肪生成受损（ppar - γ和cebp - α表达下调）。结论：低剂量G-CSF通过动员造血干细胞和诱导血管生成，成功提高了脂肪移植物的存活率。然而，高剂量G-CSF延长炎症并引起严重纤维化，导致脂肪生成受损和脂肪移植存活不良。(C) 2017年Elsevier Inc.出版。
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.