Heme oxygenase-1 gene modified human placental mesenchymal stem cells promote placental angiogenesis and spiral artery remodeling by improving the balance of angiogenic factors in vitro

Wu, Di; Liu, Yu; Liu, Xiaoxia; Liu, WeiFang; Shi, Haoran; Zhang, Yang; Zou, Li; Zhao, Yin

doi:10.1016/j.placenta.2020.07.007

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…PE was diagnosed as the definition of American College of Obstetricians and Gynecologists [ 45 ], a new onset hypertension (systolic blood pressure sustained at ≥140 mmHg or diastolic blood pressure sustained at ≥90 mmHg, or both) with proteinuria, or end organ dysfunction after 20 weeks' gestation, or both [ 2 ]. The separation method was consistent with previous reports [ 5 , 6 ]. Briefly, the placental tissue was washed twice with phosphate-buffered saline (PBS, Hyclone), the decidua and amniotic membrane were dissected apart carefully [ 46 , 47 ], and the tissue was divided into 1 mm 3 pieces.…”

Section: Methodssupporting

confidence: 91%

TLR4 Modulates Senescence and Paracrine Action in Placental Mesenchymal Stem Cells via Inhibiting Hedgehog Signaling Pathway in Preeclampsia

Zhong

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Preeclampsia (PE) is a heterogeneous disease closely associated with the accelerated senescence of the placentas. Placental mesenchymal stem cells (PMSCs) modulate placental development, which is abnormally senescent in PE together with abnormal paracrine. Both pivotal in the placenta development, Toll-like receptor 4 (TLR4) and Hedgehog (HH) pathway are also tightly involved in regulating cellular senescence. This study was aimed at demonstrating that TLR4/HH pathway modulated senescence of placentas and PMSCs in vitro and in vivo. Preeclamptic and normal PMSCs were isolated. Smoothed agonist (SAG) and cyclopamine were used to activate and inhibit HH pathway, respectively. Lipopolysaccharide (LPS) was used to activate TLR4 in vitro and establish the classic PE-like rat model. qRT-PCR, Western blotting, and immunofluorescence were used to detect the expression of TLR4 and HH components (SHH, SMO, and Gli1). Cellular biological function such as proliferation, apoptosis, and migration was compared. Cell cycle analysis, β-galactosidase staining, and the protein expressions of p16 and p53 were detected to analyze the cellular senescence. The secretion levels of human matrix metalloproteinase 9 (MMP-9) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in the conditioned medium. Cell migration, invasion, and tube formation were analyzed in HTR8/SVneo cells or human umbilical vein endothelial cells (HUVECs). Our study demonstrated that activation of TLR4 accelerated senescence of PMSCs via suppressing HH pathway both in vitro and in vivo, accompanied by the detrimental paracrine to impair the uterine spiral artery remodeling and placental angiogenesis. Meanwhile, induction of HH pathway could alleviate PE-like manifestations, improve pregnancy outcomes, and ameliorate multiorgan injuries, suggesting that strengthening the HH pathway may serve as a potential therapy in PE.

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Section: Methodssupporting

confidence: 91%

TLR4 Modulates Senescence and Paracrine Action in Placental Mesenchymal Stem Cells via Inhibiting Hedgehog Signaling Pathway in Preeclampsia

Zhong

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Localized perivascularly in placental tissues, PMSCs inextricably interacted with the components of vessel walls via paracrine mechanisms. Conditioned medium of PMSCs augmented ECs proliferation, migration, and tube formation in vitro ( Wu et al, 2020 ), which may owe to the abundant angiogenic factors at bioactive levels in PMSCs culture, including but not limited to VEGF, angiogenin, bFGF, IGF-1, insulin-like growth factor binding protein 2 (IGFBP2), IGFBP3 and IGFBP6( Kong et al, 2013 ; König et al, 2015 ; Komaki et al, 2017 ; Ma et al, 2021 ). Additionally, VCAM-1 may serve as a marker of PMSC subpopulation with superior angiogenic potential since VCAM-1 + CVMSCs population showed remarkable vasculo-angiogenic abilities both in vitro and in vivo with upregulated expression of angiogenic genes and increased secretion of proangiogenic cytokines ( Du W. et al, 2016 ).…”

Section: How Do Pmscs Play a Role In Placentation Placental Function ...mentioning

confidence: 99%

“…PMSCs may differentiate into the constitutive cells of vessel walls to initiate early placental vasculogenesis ( Boss et al, 2018 ). Besides, PMSCs interact with other component cells in the placenta via their active paracrine, thus improving the placental angiogenesis, augmenting the uterine spiral artery remolding, and modulating the uteroplacental immune status ( Magatti et al, 2019 ; Wu et al, 2020 ; Liu et al, 2021 ). Preeclamptic PMSCs have been reported to be dysfunctional and senescent with detrimental paracrine, thus playing a vital role in the development and severity of PE ( Wang et al, 2012 ; Rolfo et al, 2013 ; Ji et al, 2017 ; Nuzzo et al, 2017 ).…”

Section: Introductionmentioning

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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“…Heme oxygenase (HO)-1 is a cytoprotective, pro-angiogenic and anti-inflammatory enzyme. Human placental MSCs modified with HO-1 can promote placental angiogenesis by improving the balance of angiogenic factors (105). In ischemic skeletal muscle, human adipose-derived stromal cells expressing VEGF165 can promote angiogenesis (106).…”

Section: Application Of Angiogenesis For Cardiac Repairmentioning

confidence: 99%

Targeting angiogenesis in myocardial infarction: Novel therapeutics (Review)

Zhao

Zhu

2021

Exp Ther Med

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Heme oxygenase-1 gene modified human placental mesenchymal stem cells promote placental angiogenesis and spiral artery remodeling by improving the balance of angiogenic factors in vitro

Cited by 21 publications

References 33 publications

TLR4 Modulates Senescence and Paracrine Action in Placental Mesenchymal Stem Cells via Inhibiting Hedgehog Signaling Pathway in Preeclampsia

TLR4 Modulates Senescence and Paracrine Action in Placental Mesenchymal Stem Cells via Inhibiting Hedgehog Signaling Pathway in Preeclampsia

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

Targeting angiogenesis in myocardial infarction: Novel therapeutics (Review)

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