We previously reported that cytoprotective Heme oxygenase-1, HO-1 (HMOX1) gene-modified human placenta-derived mesenchymal stem cell (HO-1-PMSC) improved placental vascularization in vitro. In the current study, we explored the protective benefit of HO-1-PMSC transplantation in a preeclampsia (PE)-like rat model. A model of PE was successfully constructed by intraperitoneal injection of N-nitro-L-arginine methyl ester (L-NAME). Blood pressure and urinary protein levels were measured. Doppler ultrasound was examined to understand uteroplacental perfusion. ELISA was used to examine the serum levels of VEGF, PlGF, sFlt-1, and sEng. The placentas and fetuses were weighed to verify the improvement in pregnancy outcome. Immunohistochemical and H&E staining was used to detect microvessel density (MVD) in placental tissues and kidney pathology, respectively. The distribution of GFP-labeled PMSC in the placenta were observed under fluorescence microscopy. Blood pressure and proteinuria were reduced and kidney damage was improved. PE rat models treated with PMSC and HO-1-PMSC exhibited an increase in the quality of fetuses and placentas, MVD, VEGF, and PlGF expression, but substantially decreased expression of sFlt-1 and sEng. Doppler ultrasound showed that the placental perfusion was improved. Green fluorescent tracing experiments verified that the cells were successfully transplanted into the placenta and distributed in the blood vessels, indicating that the cells might participate in the process of angiogenesis. These results indicate that therapy with HO-1-PMSC could improve placental vascular dysplasia, increase placental perfusion, control PE symptoms, and promote pregnancy outcome by regulating the balance of angiogenic and antiangiogenic factors or directly participating in the repair of placental vessels in a PE-like rat model.

中文翻译：

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血红素加氧酶 1 基因修饰的人胎盘来源间充质干细胞在 N-硝基-L-精氨酸甲酯诱导的先兆子痫样大鼠模型中的保护作用：对胎盘血管生成的可能影响

我们之前报道了细胞保护性血红素加氧酶-1、HO-1 (HMOX1) 基因修饰的人胎盘衍生间充质干细胞 (HO-1-PMSC) 在体外改善了胎盘血管形成。在目前的研究中，我们探讨了 HO-1-PMSC 移植在先兆子痫 (PE) 样大鼠模型中的保护作用。腹腔注射N-硝基-L-精氨酸甲酯(L-NAME)成功构建PE模型。测量血压和尿蛋白水平。检查多普勒超声以了解子宫胎盘灌注。ELISA用于检查VEGF、PlGF、sFlt-1和sEng的血清水平。对胎盘和胎儿进行称重，以验证妊娠结局的改善。免疫组织化学和 H&E 染色用于检测胎盘组织和肾脏病理学中的微血管密度 (MVD)，分别。在荧光显微镜下观察GFP标记的PMSC在胎盘中的分布。血压和蛋白尿降低，肾脏损害得到改善。用 PMSC 和 HO-1-PMSC 处理的 PE 大鼠模型表现出胎儿和胎盘质量、MVD、VEGF 和 PlGF 表达增加，但 sFlt-1 和 sEng 表达显着降低。多普勒超声显示胎盘灌注得到改善。绿色荧光示踪实验证实细胞成功移植到胎盘并分布于血管中，表明细胞可能参与了血管生成过程。这些结果表明，HO-1-PMSC 治疗可以改善胎盘血管发育不良，增加胎盘灌注，控制 PE 症状，