Amelioration of pregnancy outcomes in a pregnant rat model with deep venous thrombosis following the transplantation of bone marrow mesenchymal stem cells.
Yuanyuan Xie, Junrong Zhang, Rong Du, Jingjing Ji, Jingjing Lu, Haoxuan Li, Yunzhao Xu, Yuquan Zhang, Xi Cheng
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引用次数: 0
Abstract
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 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.
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.
期刊介绍：
Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board.
The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology.
With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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