ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1650614
This article is part of the Research TopicAdvancements in Molecular and Cellular Mechanisms of Stem Cells in Tissue Development and RegenerationView all 9 articles
Amelioration of pregnancy outcomes in a pregnant rat model with deep venous thrombosis following the transplantation of bone marrow mesenchymal stem cells
Provisionally accepted
Yuanyuan Xie1
Junrong Zhang1
Rong Du1
Jingjing Ji1Jingjing Lu2Haoxuan Li2
Yunzhao Xu1
Yuquan Zhang1*
Xi Cheng1*- 1Affiliated Hospital of Nantong University, Nantong, China
- 2Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
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Objective 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. Methods 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 in vivo. 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 seven 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. Results 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. Conclusion 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.
Keywords: pregnancy outcomes, Angiogenesis, pregnancy-associated DVT, BM-MSCs, Placenta
Received: 20 Jun 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Xie, Zhang, Du, Ji, Lu, Li, Xu, Zhang and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuquan Zhang, Affiliated Hospital of Nantong University, Nantong, China
Xi Cheng, Affiliated Hospital of Nantong University, Nantong, China
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