RETRACTED ARTICLE: Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP

Qin, Huang; Gong, Meng; Tan, Tuantuan; Lin, Yunong; Bao, Yan; Fan, Cuifang

doi:10.1186/s11671-021-03475-5

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…Exosomal miRNAs have also presented potential as diagnostic markers and in treating PE 20 . Huang et al unraveled that human umbilical cord mesenchymal stem cell‐derived exosomal miR‐18b‐3p inhibits the development of PE symptoms in rats by targeting LEP 21 . Notably, Wang et al identified that placental exosomes derived from PE pregnant women hamper the proliferation and invasion of HTR‐8/SVneo cells, 22 and such effect may be driven by exosomal miR‐15a‐5p which regulates PI3K/AKT signaling pathway through CDK1 22 .…”

Section: Discussionmentioning

confidence: 99%

Mast cell‐derived exosomal miR‐181a‐5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP‐9 axis

Wang¹,

Chen²

2022

Clinical Laboratory Analysis

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Background Mast cells regulate the process of preeclampsia (PE). Since we previously identified mast cells specifically expressing miR‐181a‐5p in the placenta of PE patients, it is plausible to examine the effect and mechanism of mast cell‐derived exosomal miR‐181a‐5p on trophoblast cells. Methods The miR‐181a‐5p and YY1 levels were determined by quantitative real‐time reverse transcription‐polymerase chain reaction. Exosomes were identified by transmission electron microscopy, Western blot, and PKH‐26 labeling. Mast cells or trophoblast cell malignant phenotype were detected using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, wound healing, and Transwell assays. Quantification of YY1 and metastasis‐related proteins was performed using Western blot. TargetScan, JASPAR, dual‐luciferase reporter genes, and chromatin immunoprecipitation were exploited to verify the relationship between miR‐181a‐5p, YY1, and MMP‐9. Results MiR‐181a‐5p was overexpressed in mast cells of PE patients. Overexpressed miR‐181a‐5p restrained mast cell viability. Mast cell exosomes were successfully isolated, containing high expressions of CD63 and HSP70 and low expression of Calnexin and could be transported to the cytoplasm of trophoblast cells. Mast cell exosomes attenuated the viability, migration, and invasion of HTR‐8/SVneo cells, inhibited YY1, N‐cadherin, Vimentin, and MMP‐9 protein expressions, and promoted E‐cadherin protein expression. The effect of exosomes was enhanced by miR‐181a‐5p mimic but was reversed by miR‐181a‐5p inhibitor. MiR‐181a‐5p targeted YY1 which bound to the MMP‐9 promoter. Overexpressed YY1 in HTR‐8/SVneo cells accelerated the malignant phenotype of the cells and reversed the regulatory effects of exosomal miR‐181a‐5p. Conclusion Mast cell‐derived exosomal miR‐181a‐5p modulates HTR‐8/SVneo cell viability, migration, and invasion via YY1/MMP‐9.

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Section: Discussionmentioning

confidence: 99%

Mast cell‐derived exosomal miR‐181a‐5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP‐9 axis

Wang¹,

Chen²

2022

Clinical Laboratory Analysis

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“…[74, [90][91][92][93][94] ultimately may lead to an early intervention. Recent studies have found that cargo from follicle-derived exosomes includes various PCOS-specific miRNAs such as miR-373, miR-640, and miR-654-5p, with newer biomarkers being hsa-miR-1299, hsa-miR-6818-5p hsa-miR-192-5p, and hsa-miR-145-5p [66,67].…”

Section: Pre-eclampsiamentioning

confidence: 99%

The exosome: a review of current therapeutic roles and capabilities in human reproduction

Dimik

Abeysinghe

Logan

et al. 2022

Drug Deliv. and Transl. Res.

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Exosomes are nano-vesicles (30–150 nm) which may be useful as therapeutic delivery vehicles and as diagnostic biomarkers. Exosomes are produced naturally within the human body and therefore are not prone to immunogenicity effects which would otherwise destroy unelicited foreign bodies. Clinically, they have been regarded as ideal candidates for applications relating to biomarker developments for the early detection of different diseases. Furthermore, exosomes may be of interest as potential drug delivery vehicles, which may improve factors such as bioavailability of loaded molecular cargo, side effect profiles, off-target effects, and pharmacokinetics of drug molecules. In this review, the therapeutic potential of exosomes and their use as clinical biomarkers for early diagnostics will be explored, alongside exosomes as therapeutic delivery vehicles. This review will evaluate techniques for cargo loading, and the capacity of loaded exosomes to improve various reproductive disease states. It becomes important, therefore, to consider factors such as loading efficiency, loading methods, cell viability, exosomal sources, exosome isolation, and the potential therapeutic benefits of exosomes. Issues related to targeted drug delivery will also be discussed. Finally, the variety of therapeutic cargo and the application of appropriate loading methods is explored, in the context of establishing clinical utility. Graphical abstract Exosomes have more recently been widely accpeted as potential tools for disease diagnostics and the targeted delivery of certain therapeutic molecules–and in due time exosomes will be utilised more commonly within the clinical setting. Specifically, exosomal biomarkers can be identified and related to various detrimental conditions which occur during pregnancy. Considering, this review will explore the potential future of exosomes as both diagnostic tools and therapeutic delivery vehicles to treat related conditions, including the challenges which exist towards incorporating exosomes within the clinical environment to benefit patients.

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“…Additionally, the conditioned medium of PMSCs has protective effects on lipopolysaccharide-induced pregnant mice via decreasing maternal systolic blood pressure, proteinuria, sFlt-1, IL-6, and TNF-α levels ( Nuzzo et al, 2022 ). Both PMSCs transplantation and PMSCs exosome therapy could ameliorate placental vascular dysplasia, increase placental perfusion, alleviate PE symptoms, and improve pregnancy outcome by regulating the balance of the angiogenic (VEGF) and anti-angiogenic factors (sFlt-1) or directly participating in the repair of placental vessels in a PE-like rat model constructed by N-nitro- l -arginine methyl ester ( l -NAME) ( Xiong et al, 2018 ; Huang et al, 2021b ; Liu et al, 2021 ). From this, it seems that PMSCs may be a reasonable alternative approach to prevent and treat PE.…”

Section: Clinical Trials and Pe Therapies Associated With Pmscsmentioning

confidence: 99%

Significance of Placental Mesenchymal Stem Cell in Placenta Development and Implications for Preeclampsia

et al. 2022

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The well-developed placentation is fundamental for the reproductive pregnancy while the defective placental development is the pathogenetic basis of preeclampsia (PE), a dangerous complication of pregnancy comprising the leading causes of maternal and perinatal morbidity and mortality. Placenta-derived mesenchymal stem cells (PMSCs) are a group of multipotent stem cells that own a potent capacity of differentiating into constitutive cells of vessel walls. Additionally, with the paracrine secretion of various factors, PMSCs inextricably link and interact with other component cells in the placenta, collectively improving the placental vasculature, uterine spiral artery remolding, and uteroplacental interface immunoregulation. Recent studies have further indicated that preeclamptic PMSCs, closely implicated in the abnormal crosstalk between other ambient cells, disturb the homeostasis and development in the placenta. Nevertheless, PMSCs transplantation or PMSCs exosome therapies tend to improve the placental vascular network and trophoblastic functions in the PE model, suggesting PMSCs may be a novel and putative therapeutic strategy for PE. Herein, we provide an overview of the multifaceted contributions of PMSCs in early placental development. Thereinto, the intensive interactions between PMSCs and other component cells in the placenta were particularly highlighted and further extended to the implications in the pathogenesis and therapeutic strategies of PE.

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RETRACTED ARTICLE: Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-18b-3p Inhibits the Occurrence of Preeclampsia by Targeting LEP

Cited by 14 publications

References 35 publications

Mast cell‐derived exosomal miR‐181a‐5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP‐9 axis

Mast cell‐derived exosomal miR‐181a‐5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP‐9 axis

The exosome: a review of current therapeutic roles and capabilities in human reproduction

Significance of Placental Mesenchymal Stem Cell in Placenta Development and Implications for Preeclampsia

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