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

Cai, Junrong; Li, Bin; Liu, Kaiyang; Feng, Jiaxuan; Gao, Xinbo; Lu, Feng

doi:10.1016/j.bbrc.2017.07.147

Cited by 28 publications

(26 citation statements)

References 35 publications

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“…On the other hand, this study also demonstrated the significance of the pre-treatment levels of other cytokines such as G-CSF with RILF2 in NSCLC patients though they were not into the SVM model achieved by the machine learning algorithm. In mice that received a high-dose G-CSF for 7 consecutive days right after autologous fat grafting, high-dose G-CSF injection was found to have a prolonged macrophage infiltration and elevated levels of inflammation, which could be the direct cause of severe fibrosis ( 31 ). Future studies are needed to define the contribution CLL4 and G-CSF to RILF as well external validate our results.…”

Section: Discussionmentioning

confidence: 99%

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients

Lam

et al. 2021

Front. Oncol.

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BackgroundRadiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.MethodsThis is a secondary analysis of prospective studies from two academic cancer centers. The primary endpoint was grade≥2 (RILF2), classified according to a system consistent with the consensus recommendation of an expert panel of the AAPM task for normal tissue toxicity. Eligible patients must have at least 6 months’ follow-up after radiotherapy commencement. Baseline levels of 30 cytokines, dosimetric, and clinical characteristics were analyzed. Support vector machine (SVM) algorithm was applied for model development. Data from one center was used for model training and development; and data of another center was applied as an independent external validation.ResultsThere were 57 and 37 eligible patients in training and validation datasets, with 14 and 16.2% RILF2, respectively. Of the 30 plasma cytokines evaluated, SVM identified baseline circulating CCL4 as the most significant cytokine associated with RILF2 risk in both datasets (P = 0.003 and 0.07, for training and test sets, respectively). An SVM classifier predictive of RILF2 was generated in Cohort 1 with CCL4, mean lung dose (MLD) and chemotherapy as key model features. This classifier was validated in Cohort 2 with accuracy of 0.757 and area under the curve (AUC) of 0.855.ConclusionsUsing machine learning, this study constructed and validated a weighted-SVM classifier incorporating circulating CCL4 levels with significant dosimetric and clinical parameters which predicts RILF2 risk with a reasonable accuracy. Further study with larger sample size is needed to validate the role of CCL4, and this SVM classifier in RILF2.

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Section: Discussionmentioning

confidence: 99%

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients

Lam

et al. 2021

Front. Oncol.

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“…Researchers have found that in ammation could inhibit adipogenesis [29]. Moreover, overactivation of in ammation reduces the survival rate of fat transplantation [11,30,31]. Therefore, salvianolic acid B may have an antiin ammatory effect in fat transplantation, although this supposition requires more in-depth research.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid-B improves fat graft survival by promoting proliferation and adipogenesis

Sun¹,

Ho²,

Gao³

et al. 2021

Preprint

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Background: Our previous study proved that Salvia miltiorrhiza could enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza, on fat graft survival has not yet been investigated.Objective: This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied.Methods: In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival.Results: In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis.Conclusions: Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.

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“…However, it has been noted that one side effect of this adjuvant treatment is an increase in tumor angiogenesis in some, but not all, patients (Shojaei et al, 2009;Voloshin et al, 2011;Aliper et al, 2014). Several studies have demonstrated the pro-angiogenic effect of G-CSF, likely via the recruitment of endothelial progenitor cells, but this effect appears to be site and dose specific, and interaction with the local microenvironment also plays a significant role in this effect (Sato et al, 2008;Cai et al, 2017;Li et al, 2019). Very few studies have investigated the effects of G-CSF on VSMC biology, with differing results.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Promotes Trophoblast Cell Induced Separation of Vascular Smooth Muscle Cells in Vascular Remodeling via Induction of G-CSF

Zhang

Chen

et al. 2020

Front. Cell Dev. Biol.

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Vitamin D deficiency is associated with complications of pregnancy such as pre-eclampsia, fetal growth restriction, and miscarriage, all of which are also associated with incomplete spiral artery (SpA) remodeling. We have previously shown that both uterine natural killer (uNK) cells and extravillous trophoblast cells (EVT) are required for successful SpA remodeling, but whether their activity in this process is modulated by vitamin D is not known. In the current study, we use a previously described chorionic plate artery (CPA) ex vivo model of vascular remodeling to determine the effects of 1,25(OH)2D treated uNK cell, placental explant (PEx), and uNK/PEx conditioned medium (CM) on vascular smooth muscle cell (VSMC) disorganization and phenotypic switching. Significant results were followed up in VSMCs in vitro. We demonstrate that 1,25(OH)2D can enhance the ability of PEx to induce SpA remodeling, via a mechanism associated with increased secretion of granulocyte-colony stimulating factor (G-CSF). G-CSF appears able to increase VSMC disorganization and phenotypic switching in both an ex vivo vascular model and in vitro VSMC cultures. The clinical relevance of these findings are still to be determined. G-CSF may have differential effects depending on dose and vascular bed, and vitamin D may play a role in potentiating these actions. G-CSF may be an interesting potential therapeutic target for facilitating physiological vascular remodeling for the prevention of adverse obstetric outcomes.

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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

Cited by 28 publications

References 35 publications

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients

Salvianolic acid-B improves fat graft survival by promoting proliferation and adipogenesis

Vitamin D Promotes Trophoblast Cell Induced Separation of Vascular Smooth Muscle Cells in Vascular Remodeling via Induction of G-CSF

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