ABSTRACT
OBJECTIVES@#To explore the effect of hydrogel loaded with exosomes from Wharton's Jelly-derived mesenchymal stem cell (WJMSC) on wound healing.@*METHODS@#Exosomes were extracted from WJMSC, and the morphology and size of WJMSC-derived exosomes (WEX) were analyzed by transmission electron microscopy and nanoparticle size analyzer, respectively. The surface markers CD9, CD81, and Calnexin of WEX were detected by Western blotting. Exosome-loaded alginate hydrogel (WEX-gel) was prepared; its morphology was studied by scanning electron microscope, and its rheological behavior was examined by a rheometer. The in vitro drug release performance of WEX-gel was investigated by BCA method. RAW264.7 cells were treated with alginate hydrogel, WEX and WEX-gel, respectively; and the expression of CD86 and CD206 in macrophages was detected by flow cytometry. A full-thickness skin wound model was established in mice; the model mice were randomly divided into blank control group, WEX control group and WEX-gel group, and PBS, WEX and WEX-gel were applied to the wound area of mice, respectively. On day 3, the skin tissue of mice was excised, and the antibacterial effect of WEX hydrogel was evaluated by plate counting. On day 15, the mice were euthanized and the percentage of residual wounds was calculated. The histological changes of the skin wound were observed after hematoxylin and eosin (HE) and Masson stainings. The expression of CD86, CD206, CD31 and vascular endothelial growth factor (VEGF) in the skin wound tissue was detected by immunohistochemistry.@*RESULTS@#Exosomes were successfully extracted from WJMSC. WEX-gel presented a regular three-dimensional network structure, good rheology and controlled drug release performance. WEX-gel promoted the polarization of RAW264.7 cells from the M1 phenotype to M2 phenotype in vitro. The residual wound percentage in blank control group, WEX control group and WEX-gel group were (27.5±3.4)%, (15.3±1.2)% and (7.6±1.1)%, respectively (P<0.05). The antibacterial property of WEX-gel is better than that of WEX (P<0.05). The dermis thickness, the number of new hair follicles, and the rate of collagen deposition in the WEX-gel group were significantly higher than those in the other two groups (all P<0.05). The expression of CD206, CD31 and VEGF in skin wound tissue was higher and the expression of CD86 was lower in WEX-gel group than those in other two groups (all P<0.05).@*CONCLUSIONS@#WEX-gel can significantly promote wound healing in mice by regulating the polarization of macrophages.
Subject(s)
Mice , Animals , Vascular Endothelial Growth Factor A , Wharton Jelly , Exosomes , Hydrogels , Wound Healing/physiology , Mesenchymal Stem Cells , Anti-Bacterial Agents , AlginatesABSTRACT
Objective To evaluate FIB-NLR,a combined neutrophil-lymphocyte ratio (NLR) and fibrinogen concentration (FIB) in predicting the prognosis of gastrointestinal stromal tumors (GIST).Methods Data of 79 GIST patients who underwent surgery from Jun 2010 to Dec 2014 were retrospectively analyzed.Patients were divided into 3 groups:NLR ＜ 2.30 and FIB ＜ 3.85 g/L were defined as group 0,NLR≥2.30 and FIB ＜3.85 g/L or NLR ＜2.30 and FIB≥3.85 g/L as group 1,NLR≥2.30 and FIB≥3.85 g/L as group 2.The clinicopathological features of the three groups and the 5-year recurrence-free survival rate after surgery were compared.Results FIB concentration and NLR were significantly correlated with NIH risk grade and tumor size in GIST patients (x2 =9.517,12.41 1,6.081,20.067,all P ＜ 0.05).FIB-NLR was closely related to tumor size,tumor risk and tumor mitosis (x2 =14.406,12.514,28.225,all P ＜ 0.05).Survival analysis showed that high FIB predicts lower 5-year recurrence-free survival rate,it was 87.4％ for group 0,60.8％ for group 1,21.1％ for group2,x2 =29.617,P＜0.000).Conclusion FIB-NLR independently predicts the prognosis of gastrointestinal stromal tumors.
