Human umbilical cord mesenchymal stem cells improve the pregnancy outcomes of preeclampsia rats via inducing placental angiogenesis
Panpan Zhao, Yuchen Zhang, Guang Zhang, Huan Niu, Jiao Jiao Li, Ruochen Hao, Mingkun Xie, Shuhui Chu, Xinyi Li, Genxia Li
Abstract
BACKGROUND: Preeclampsia is considered to be a serious complication unique to pregnancy caused by placental dysplasia. Although interventions such as antihypertensive drugs and magnesium sulfate can partially mitigate maternal risk, the ultimate remedy remains delivery. In recent years, mesenchymal stem cells (MSCs) have become promising therapeutic approach in the treatment of ischemic diseases. Therefore, this study aimed to investigate the effect of human umbilical cord mesenchymal stem cells (hucMSCs) on pregnancy outcomes and placental angiogenesis in N-nitro-L-arginine methyl ester (L-NAME) induced preeclampsia rats. METHODS: The expression of mesenchymal markers in hucMSCs was analyzed by flow cytometry. Multipotent differentiation of hucMSCs was identified, respectively. HucMSCs were injected into the preeclampsia rat by the tail vein. SBP was measured at the rat tail artery using an automatic noninvasive blood pressure monitor. The proteinuria levels were measured using the BCA method. RT-qPCR and ELISA were used to assess the mRNA expression and plasma concentrations of soluble FMS-like tyrosine kinase 1 (sFlt-1), placental growth factor (PLGF), and vascular endothelial growth factor (VEGF). Placental tissues were collected for immunohistochemistry and pathological analysis. RESULTS: HucMSCs were positive for CD90, CD73, and CD105, and could differentiate into osteoblasts, adipocytes and chondrocytes. PE rats treated with hucMSCs showed a lowering of SBP and proteinuria and a higher fetal and placental mass. The microvascular density (MVD), mRNA expression, and plasma concentrations of VEGF and PLGF were increased in the hucMSCs-treated group, while the sFlt-1 levels were decreased. CONCLUSION: HucMSCs may promote placental angiogenesis and improve the pregnancy outcomes of preeclampsia rats by regulating the balance of pro-angiogenic and antiangiogenic factors.