BackgroundSevere burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism.MethodsAdult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI), and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA.ResultsWe found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation.ConclusionThe study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

The abilities of intelligent polymer hydrogels to change their structure and volume phase in response to external stimuli have provided new possibilities for various advanced technologies and great research and application potentials in the medical field. The natural polymer-based hydrogels have the advantages of environment-friendliness, rich sources and good biocompatibility. Based on their responsiveness to external stimuli, the natural polymer-based hydrogels can be classified into the temperature-responsive hydrogel, pH-responsive hydrogel, light-responsive hydrogel, electricresponsive hydrogel, redox-responsive hydrogel, enzyme-responsive hydrogel, magnetic-responsive hydrogel, multi-responsive hydrogel, etc. In this review, we have compiled some recent studies on natural polymer-based stimuli-responsive hydrogels, especially the hydrogels prepared from polysaccharides. The preparation methods, properties and applications of these hydrogels in the medical field are highlighted.

Burn wound progression is caused by many mechanisms including local tissue hypoperfusion, prolonged inflammation, free radical damage, apoptosis, and necrosis in burn wounds. Autophagy, a homeostatic process by which cells break down their own components, was found to protect against ischemic injury, inflammatory diseases, and apoptosis in some cases. We tested whether rapamycin, an autophagy inducer, could ameliorate burn wound progression and promote wound healing through autophagy enhancement. Using a previously described deep second-degree burn model, we first tested the effects of rapamycin on autophagic response in burn wound tissue. Autophagy levels in wound tissue of treated rats were increased as compared with controls. Furthermore, we found that laser Doppler flowmetry values and Na/K-ATPase activities were markedly higher in the treated wounds. The content of interleukin-8, methane dicarboxylic aldehyde, and myeloperoxidase activity in the wounds of treated rats were much lower than in controls. The apoptotic rates in treated wounds were much lower than controls as determined by terminal deoxynucleotidyl transferase mediated nick end labeling assay. Finally, histomorphological analysis showed that burn wound progression in the treatment group was ameliorated. The time to wound reepithelialization was shorter in the treated wounds than controls 22.5 ± 1.4 days vs. 24.8 ± 1.3 days (mean ± standard deviation, p < 0.01).

Hyperglycemia is one of the most important clinical features of burn patients. Previous reports had demonstrated that miRNA was involved in regulating glucose metabolism in various diseases such as diabetes and obesity. Our current study discovered the relationship between miR-194 and hyperglycemia in burn rats via suppressing insulin-like growth factor 1 receptor (IGF-IR). We found that the fasting blood glucose was significantly increased in rats of the burn group, and protein expression of IGF-IR was attenuated in response to burn injury. Similar to the results of animal experiments, miR-194 expression was significantly elevated and IGF-IR protein level was suppressed in L6 cells treated with serum from burn rats compared with those treated by serum from sham rats. However, IGF-IR mRNA level was comparable between burn and sham rats, suggesting that IGF-IR may be downregulated at the translation level. Further experiments revealed that miR-194 was significantly increased in burn rats compared with sham rats using miRNA array and real-time polymerase chain reaction (PCR) assay. And IGF-IR protein expression was reduced in L6 cells transfected with miR-194 plasmid. Insulin-like growth factor 1 receptor expression was also repressed and fasting blood glucose was increased in rats injected with miR-194 plasmid. In general, we have identified a novel function of miR-194 in modulating burn-induced hyperglycemia via suppressing the expression of IGF-IR.

Severe burns are typically followed by hypermetabolism characterized by significant muscle wasting, which causes considerable morbidity and mortality. The aim of the present study was to explore the underlying mechanisms of skeletal muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4-phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER), burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1, 4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for transmission electron microscopy, calcium imaging, gene expression and protein analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain activity measurement. The results showed that ER stress markers were increased in the burn group compared with the sham group, especially at post-burn days 4 and 7, which might consequently elevate cytoplasmic calcium concentration, promote calpain production as well as activation, and cause skeletal muscle damage/wasting of TA muscle after severe burn injury. Interestingly, treatment with 4-PBA prevented burn-induced ER swelling and altered protein expression of ER stress markers and calcium release, attenuating calpain activation and skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3-I ratio were also increased in the burn group compared with the sham group, while MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken together, these findings suggested that severe burn injury induces ER stress, which in turns causes calpain activation. ER stress and subsequent activated calpain play a critical role in skeletal muscle damage/wasting in burned rats.