Xie Yuanyuan, Zhang Junrong, Du Rong, Ji Jingjing, Lu Jingjing, Li Haoxuan, Xu Yunzhao, Zhang Yuquan, Cheng Xi
Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Front Cell Dev Biol. 2025 Sep 4;13:1650614. doi: 10.3389/fcell.2025.1650614. eCollection 2025.
We investigated the effects of bone marrow mesenchymal stem cells (BM-MSCs) on pregnancy outcomes in pregnant Sprague-Dawley rats with deep venous thrombosis (DVT) and explored the potential mechanisms involved.
Eighteen pregnant rats were randomly divided into three groups: sham, DVT and BM-MSCs. The BM-MSCs were transfected with lentivirus carrying luciferase and cell membrane staining reagent CM-Dil to analyze the location and survival of BM-MSCs . We also compared the weight and length of the thrombus, the embryo absorption rate, the complete blood count, coagulation function, and D-dimer concentration of pregnant rats between the groups. Thereafter, placental blood flow was monitored by Doppler ultrasound and the number of placental blood vessels was determined by CD31 staining 7 days following BM-MSC transplantation. Finally, the expression of placental growth factor (PlGF), vascular endothelial growth factor A (VEGFA), soluble fms-like tyrosine kinase 1 (sFlt1), VEGF receptor 2 (VEGFR2) both in mRNA and protein levels were detected.
Reduced thrombus and improved pregnancy outcomes were observed in the BM-MSCs group. Furthermore, BM-MSCs survived and migrated to the lungs, liver, spleen, and thrombotic tissues, rather than the placenta. Doppler ultrasound indicated insufficient placental perfusion in the DVT group, which was reversed by the transplantation of BM-MSCs. BM-MSCs promoted placental angiogenesis by upregulating VEGFA and VEGFR2, and by reducing sFlt1 protein levels in the placenta.
Our analysis suggested that BM-MSCs improve pregnancy outcomes associated with obstetric DVT by alleviating placental hypoperfusion and regulating the balance of placental pro-/anti-angiogenic factors.
我们研究了骨髓间充质干细胞（BM-MSCs）对患有深静脉血栓形成（DVT）的妊娠Sprague-Dawley大鼠妊娠结局的影响，并探讨了其中涉及的潜在机制。
将18只妊娠大鼠随机分为三组：假手术组、DVT组和BM-MSCs组。用携带荧光素酶的慢病毒和细胞膜染色试剂CM-Dil转染BM-MSCs，以分析BM-MSCs的定位和存活情况。我们还比较了各组妊娠大鼠血栓的重量和长度、胚胎吸收率、全血细胞计数、凝血功能以及D-二聚体浓度。此后，在BM-MSC移植后7天，通过多普勒超声监测胎盘血流，并通过CD31染色确定胎盘血管数量。最后，检测胎盘生长因子（PlGF）、血管内皮生长因子A（VEGFA）、可溶性fms样酪氨酸激酶1（sFlt1）、VEGF受体2（VEGFR2）在mRNA和蛋白质水平的表达。
在BM-MSCs组中观察到血栓减少和妊娠结局改善。此外，BM-MSCs存活并迁移至肺、肝、脾和血栓形成组织，而非胎盘。多普勒超声显示DVT组胎盘灌注不足，而BM-MSCs移植可使其逆转。BM-MSCs通过上调VEGFA和VEGFR2以及降低胎盘中sFlt1蛋白水平促进胎盘血管生成。
我们的分析表明，BM-MSCs通过减轻胎盘灌注不足和调节胎盘促/抗血管生成因子的平衡来改善与产科DVT相关的妊娠结局。
