The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity

Abstract Background An environment of gestational diabetes mellitus (GDM) can modify the phenotype of stem cell populations differentially according to their placental localization, which can be useful to study the consequences for the fetus. We sought to explore the effect of intrauterine GDM exposure on the angiogenic properties of human amniotic membrane stem cells (hAMSCs). Methods We comprehensively characterized the angiogenic phenotype of hAMSCs isolated from 14 patients with GDM and 14 controls with normal glucose tolerance (NGT). Maternal and fetal parameters were also recorded. Hyperglycemia, hyperinsulinemia and palmitic acid were used to in vitro mimic a GDM-like pathology. Pharmacological and genetic inhibition of protein function was used to investigate the molecular pathways underlying the angiogenic properties of hAMSCs isolated from women with GDM. Results Capillary tube formation assays revealed that GDM-hAMSCs produced a significantly higher number of nodes (P = 0.004), junctions (P = 0.002) and meshes (P < 0.001) than equivalent NGT-hAMSCs, concomitant with an increase in the gene/protein expression of FGFR2, TGFBR1, SERPINE1 and VEGFA. These latter changes were recapitulated in NGT-hAMSCs exposed to GDM-like conditions. Inhibition of the protein product of SERPINE1 (plasminogen activator inhibitor 1, PAI-1) suppressed the angiogenic properties of GDM-hAMSCs. Correlation analyses revealed that cord blood insulin levels in offspring strongly correlated with the number of nodes (r = 0.860; P = 0.001), junctions (r = 0.853; P = 0.002) and meshes (r = 0.816; P = 0.004) in tube formation assays. Finally, FGFR2 levels correlated positively with placental weight (r = 0.586; P = 0.028) and neonatal adiposity (r = 0.496; P = 0.014). Conclusions GDM exposure contributes to the angiogenic abilities of hAMSCs, which are further related to increased cord blood insulin and fetal adiposity. PAI-1 emerges as a potential key player of GDM-induced angiogenesis.

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Human Amniotic Membrane as a Matrix for Endothelial Differentiation of VEGF-Treated Dental Stem Cells

Cellular and Molecular Bioengineering ◽

10.1007/s12195-019-00596-x ◽

2019 ◽

Vol 12 (6) ◽

pp. 599-613 ◽

Cited By ~ 1

Author(s):

Siti Nurnasihah Md Hashim ◽

Muhammad Fuad Hilmi Yusof ◽

Wafa’ Zahari ◽

Hamshawagini Chandra ◽

Khairul Bariah Ahmad Amin Noordin ◽

...

Keyword(s):

Stem Cells ◽

Amniotic Membrane ◽

Endothelial Differentiation ◽

Human Amniotic Membrane ◽

Dental Stem Cells

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The effect of different concentrations of iron oxide nanoparticles on the expression of p53 gene in human amniotic membrane-derived mesenchymal stem cells

Nova Biologica Reperta ◽

10.52547/nbr.7.3.256 ◽

2020 ◽

Vol 7 (3) ◽

pp. 256-266

Author(s):

Neda Tekiyeh Maroof ◽

◽

Nahid Aboutaleb ◽

Maryam Naseroleslami ◽

◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Iron Oxide ◽

Iron Oxide Nanoparticles ◽

Amniotic Membrane ◽

P53 Gene ◽

Oxide Nanoparticles ◽

Human Amniotic Membrane

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Human amniotic membrane‐mesenchymal stem cells‐conditioned medium reduces inflammatory factors and fibrosis in ovalbumin‐induced asthma in mice

Experimental Physiology ◽

10.1113/ep088911 ◽

2020 ◽

Author(s):

Fereshteh Dalouchi ◽

Raza Falak ◽

Morteza Bakhshesh ◽

Zeynab Sharifi Aghdam ◽

Yaser Azizi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Amniotic Membrane ◽

Inflammatory Factors ◽

Human Amniotic Membrane

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Anti-Inflammatory and Anti-Fibrotic Effects of Human Amniotic Membrane Mesenchymal Stem Cells and Their Potential in Corneal Repair

Stem Cells Translational Medicine ◽

10.1002/sctm.18-0042 ◽

2018 ◽

Vol 7 (12) ◽

pp. 906-917 ◽

Cited By ~ 24

Author(s):

Alejandro Navas ◽

Fátima Sofía Magaña-Guerrero ◽

Alfredo Domínguez-López ◽

César Chávez-García ◽

Graciela Partido ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Amniotic Membrane ◽

Human Amniotic Membrane ◽

Anti Inflammatory

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Human Amniotic Membrane Improves Healing in a Chronic, Massive Rotator Cuff Repair Model

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967118s00167 ◽

2018 ◽

Vol 6 (7_suppl4) ◽

pp. 2325967118S0016 ◽

Cited By ~ 1

Author(s):

David Kovacevic ◽

Robert Suriani ◽

Maarouf Saad ◽

Steven Tommasini ◽

Christopher Mendias ◽

...

Keyword(s):

Gene Expression ◽

Rotator Cuff ◽

Amniotic Membrane ◽

Human Amniotic Membrane ◽

Muscle Repair ◽

Sectional Area ◽

Cross Sectional ◽

Rotator Cuff Muscle ◽

Injury And Repair ◽

Pai 1

Objectives: Rotator cuff tendon heals by fibrovascular scar that is weaker than native tissue leading to repairs that are prone to failure. Our objective was to investigate the ability of an amniotic membrane-derived human allograft to improve rotator cuff tendon-bone healing and skeletal muscle architecture in a chronic massive rotator cuff injury and repair model in rats. We hypothesized that application of human amniotic membrane to the tendon-bone interface at the time of repair will result in increased attachment strength and rotator cuff muscle fiber force secondary to improved bone formation and nthesis histomorphometry, less plasminogen activator inhibitor-1 (PAI-1) expression, and induced muscle repair gene expression. Methods: Eighty-five male Sprague-Dawley rats were allocated to one of four groups: (1) uninjured (U), (2) injury only (IO), (3) chronic injury and repair (CR), or (4) chronic injury and augmented repair (ER). The IO, CR, and ER groups underwent unilateral detachment of the supraspinatus and infraspinatus tendons with injection of the corresponding muscle with 3 u/kg Onabotulinum toxin A. Four weeks following injury, a surgical repair was performed in the CR and ER groups using transosseous suture fixation with human amniotic membrane applied to the tendon-bone repair site in the ER group. Animals were euthanized at four weeks following the repair. Biomechanical testing of the supraspinatus and infraspinatus tendon-bone complex and single fiber contractility testing of the supraspinatus muscle were performed. Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometric quantification of fibrocartilage formation and collagen organization, and immunostaining with PAI-1. The rotator cuff muscle was evaluated with immunohistochemical localization for lipid deposition and total cross-sectional area. Real-time polymerase chain reaction evaluated relative expression of genes relevant to muscle repair. Statistical analysis was performed using a nonparametric Kruskal-Wallis test with significance set at p<0.05. Results: Augmentation with amniotic membrane did not lead to increased load-to-failure or stiffness compared to CR. The cross-sectional area, maximum isometric force, and specific force of individual supraspinatus muscle fibers were significantly greater with ER compared to CR (Figure 1). Microcomputed tomography revealed a larger volume of newly formed bone present at the bony footprint with ER compared to CR. Histomorphometric analysis demonstrated significantly greater fibrocartilage area and collagen organization at the healing tendon-bone insertion site with ER compared to CR at 4 week. Qualitatively, there was less PAI-1 immunostaining noted at the tendon-bone interface in the ER group. There was less lipid deposition and greater cross-sectional area of the rotator cuff muscle fibers in the ER group. Rotator cuff muscle gene expression with ER demonstrated a downregulation of apoptosis regulatory genes BCL2 and Caspase-3, adipogenesis regulatory genes FITM1 and FITM2, TNF-alpha and TGF-beta 3 compared to CR. Conclusion: Augmentation with human amniotic membrane in a chronic, massive rotator cuff injury and repair model led to greater bone formation, more organized tendon enthesis, induced muscle repair gene expression, and greater rotator cuff muscle fiber force secondary to less PAI-1 expression.

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Developmental Expression of Plasminogen Activator Inhibitor-1 Associated With Thrombopoietin-Dependent Megakaryocytic Differentiation

Blood ◽

10.1182/blood.v94.2.475 ◽

1999 ◽

Vol 94 (2) ◽

pp. 475-482 ◽

Cited By ~ 12

Author(s):

Seiji Madoiwa ◽

Norio Komatsu ◽

Jun Mimuro ◽

Kouzoh Kimura ◽

Michio Matsuda ◽

...

Keyword(s):

Cord Blood ◽

Mrna Expression ◽

Progenitor Cells ◽

Plasminogen Activator ◽

Messenger Rna ◽

Plasminogen Activator Inhibitor ◽

Developmental Expression ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

Abstract Plasminogen activator inhibitor-1 (PAI-1) is present in the platelet -granule and is released on activation. However, there is some debate as to whether the megakaryocyte and platelet synthesize PAI-1, take it up from plasma, or both. We examined the expression of PAI-1 in differentiating megakaryocytic progenitor cells (UT-7) and in CD34+/CD41− cells from cord blood. UT-7 cells differentiated with thrombopoietin (TPO) resembled megakaryocytes (UT-7/TPO) with respect to morphology, ploidy, and the expression of glycoprotein IIb-IIIa. PAI-1 messenger RNA (mRNA) expression was upregulated and PAI-1 protein synthesized in the UT-7/TPO cells accumulated in the cytoplasm without being released spontaneously. In contrast, erythropoietin (EPO)-stimulated UT-7 cells (UT-7/EPO) did not express PAI-1 mRNA after stimulation with TPO because they do not have endogenous c-Mpl. After cotransfection with human wild-typec-mpl, the cells (UT-7/EPO-MPL) responded to phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor- (TNF-), and interleukin-1β (IL-1β) with enhanced PAI-1 mRNA expression within 24 to 48 hours. However, induction of PAI-1 mRNA in UT-7/EPO-MPL cells by TPO required at least 14-days stimulation. UT-7/EPO cells expressing c-Mpl changed their morphology and the other characteristics similar to the UT-7/TPO cells. TPO also differentiated human cord blood CD34+/CD41− cells to CD34−/CD41+ cells, generated morphologically mature megakaryocytes, and induced the expression of PAI-1 mRNA. These results suggest that both PAI-1 mRNA and de novo PAI-1 protein synthesis is induced after differentiation of immature progenitor cells into megakaryocytes by TPO.

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