Fu Lihua, Liu Yongjun, Zhang Dan, Xie Jiang, Guan Hongbo, Shang Tao
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China ; Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China.
The Enterprise Key Laboratory of Tianjin Stem Cell Regenerative and Translational Medicine, Tianjin 300300, P.R. China.
Exp Ther Med. 2015 Nov;10(5):1851-1856. doi: 10.3892/etm.2015.2742. Epub 2015 Sep 11.
Mesenchymal stem cells (MSCs), which exhibit the property of immune-modulation, have been shown to treat various diseases, including pulmonary hypertension. There is a functional similarity between the pulmonary circulation and the placenta, but it remains to be elucidated whether MSCs can be applied to treat endotoxin-induced hypertension during pregnancy; therefore, the aim of the present study was to investigate the therapeutic effect of a human umbilical cord-derived MSC infusion on endotoxin-induced hypertension during pregnancy. Rats were randomly divided into three groups (n=7 per group): Control, endotoxin-treated and endotoxin + MSCs. The model of preeclampsia (PE) was established via the intravenous injection of endotoxin. In the endotoxin + MSCs group, MSCs at 2×10 cells/rat were injected via the vena caudalis. The blood pressure, urine protein and number of white blood cells were measured. In addition, the protein expression levels of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine IL-10 were examined by ELISA. The blood pressure, levels of urine protein and number of white blood cells in the endotoxin-treated group were significantly higher than those in the control group (P<0.05); however, this increase was significantly attenuated in the endotoxin + MSCs group (P<0.05). In addition, the application of MSCs significantly reduced the levels of pro-inflammatory TNF-α and IL-1β and increased the levels of anti-inflammatory IL-10 in the endotoxin-treated rats. In conclusion, umbilical cord-derived MSCs have a protective effect in an endotoxin-induced model of PE, and this effect is likely elicited through the suppression of inflammatory factors. Umbilical cord-derived MSC-based therapy may provide a potential therapeutic method for endotoxin-induced hypertension during pregnancy.
间充质干细胞(MSCs)具有免疫调节特性,已被证明可治疗多种疾病,包括肺动脉高压。肺循环和胎盘之间存在功能相似性,但MSCs是否可用于治疗孕期内毒素诱导的高血压仍有待阐明;因此,本研究的目的是探讨人脐带间充质干细胞输注对孕期内毒素诱导的高血压的治疗效果。将大鼠随机分为三组(每组n = 7):对照组、内毒素处理组和内毒素+间充质干细胞组。通过静脉注射内毒素建立子痫前期(PE)模型。在内毒素+间充质干细胞组中,以2×10个细胞/大鼠的剂量经尾静脉注射间充质干细胞。测量血压、尿蛋白和白细胞数量。此外,通过酶联免疫吸附测定法检测促炎细胞因子白细胞介素(IL)-1β和肿瘤坏死因子-α(TNF-α)以及抗炎细胞因子IL-10的蛋白表达水平。内毒素处理组的血压、尿蛋白水平和白细胞数量显著高于对照组(P<0.05);然而,在内毒素+间充质干细胞组中,这种升高显著减弱(P<0.05)。此外,间充质干细胞的应用显著降低了内毒素处理大鼠中促炎TNF-α和IL-1β的水平,并提高了抗炎IL-10的水平。总之,脐带间充质干细胞在PE内毒素诱导模型中具有保护作用,这种作用可能是通过抑制炎症因子引发的。基于脐带间充质干细胞的治疗可能为孕期内毒素诱导的高血压提供一种潜在的治疗方法。