Jin Wang, Zhao Yiming, Hu Yonghao, Yu Dingding, Li Xiang, Qin Yafei, Kong Dejun, Wang Hao
Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China.
Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China.
Stem Cells Int. 2020 Mar 17;2020:4820543. doi: 10.1155/2020/4820543. eCollection 2020.
Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells obtained from human menstrual blood, whose positive therapeutic effects have been validated in several experimental models. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, plays an important role in the migration of mesenchymal stromal cells. The purpose of this study was to investigate the role of the SDF-1/CXCR4 pathway in the therapeutic effects of ERCs in a mouse sepsis model. Through preexperiment and confirmation, wild-type C57BL/6 mice were intraperitoneally injected with 10 mg/kg lipopolysaccharide (LPS). The therapeutic effects of ERCs with different pretreatments were evaluated by assessing sepsis-related symptoms, detecting tissue damage and measuring levels of inflammatory and oxidative stress-related factors. The experiments demonstrated that there was a much higher CXCR4 expression on ERCs when they were cocultured with SDF-1. The experiment results showed that SDF-1 expression significantly increased in mouse tissues. Further experiments also confirmed that, compared with the unmodified ERC treatment group, SDF-1 pretreatment significantly enhanced the therapeutic effects of ERCs on alleviating sepsis symptoms, ameliorating pathological changes, reducing Bax level, and increasing Bcl-2 and PCNA expressions in mouse liver tissues. Furthermore, it was also found that SDF-1-pretreated ERCs contributed to reducing the levels of proinflammatory cytokines (TNF-, IL-1) and increasing the levels of anti-inflammatory factors (IL-4, IL10) in mouse serum, liver, and lung. Moreover, SDF-1-pretreated ERCs could also significantly decrease the levels of iNOS and MDA and increase the expression of Nrf2, HO-1, and SOD in liver tissues. Taken together, these results indicate that SDF-1 pretreatment plays a key role in improving the therapeutic effects of ERCs in alleviating sepsis-related symptoms, reducing tissue damage, regulating inflammatory imbalance, and relieving oxidative stress in a mouse sepsis model, which provides more possibilities for the clinical application of ERCs in sepsis and relevant diseases.
子宫内膜再生细胞（ERCs）是从人月经血中获得的间充质样基质细胞，其积极的治疗效果已在多个实验模型中得到验证。基质细胞衍生因子-1（SDF-1）是CXCR4的配体，在间充质基质细胞的迁移中起重要作用。本研究的目的是探讨SDF-1/CXCR4通路在小鼠脓毒症模型中ERCs治疗效果中的作用。通过预实验和确认，将野生型C57BL/6小鼠腹腔注射10mg/kg脂多糖（LPS）。通过评估脓毒症相关症状、检测组织损伤以及测量炎症和氧化应激相关因子水平，来评估不同预处理的ERCs的治疗效果。实验表明，当ERCs与SDF-1共培养时，其CXCR4表达要高得多。实验结果显示，小鼠组织中SDF-1表达显著增加。进一步实验还证实，与未修饰的ERCs治疗组相比，SDF-1预处理显著增强了ERCs在减轻小鼠脓毒症症状、改善病理变化、降低Bax水平以及增加小鼠肝脏组织中Bcl-2和PCNA表达方面的治疗效果。此外，还发现SDF-1预处理的ERCs有助于降低小鼠血清、肝脏和肺中促炎细胞因子（TNF-、IL-1）的水平，并增加抗炎因子（IL-4、IL10）的水平。此外，SDF-1预处理的ERCs还可显著降低肝脏组织中iNOS和MDA的水平，并增加Nrf2、HO-1和SOD的表达。综上所述，这些结果表明，SDF-1预处理在改善ERCs在减轻小鼠脓毒症相关症状、减少组织损伤、调节炎症失衡以及缓解氧化应激方面的治疗效果中起关键作用，这为ERCs在脓毒症及相关疾病中的临床应用提供了更多可能性。
