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

  • Datos identificativos

    Identificador: imarina:9241954
    Autores:
    Klid, SergiyAlgaba-Chueca, FranciscoMaymo-Masip, ElsaGuarque, AlbertBallesteros, MonicaDiaz-Perdigones, CristinaGutierrez, CristinaVendrell, JoanMegia, AnaFernandez-Veledo, Sonia
    Resumen:
    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 contribute
  • Otros:

    Autor según el artículo: Klid, Sergiy; Algaba-Chueca, Francisco; Maymo-Masip, Elsa; Guarque, Albert; Ballesteros, Monica; Diaz-Perdigones, Cristina; Gutierrez, Cristina; Vendrell, Joan; Megia, Ana; Fernandez-Veledo, Sonia;
    Departamento: Bioquímica i Biotecnologia Medicina i Cirurgia
    Autor/es de la URV: Ballesteros Pérez, Monica / GUTIÉRREZ FORNÉS, CRISTINA / Klid Klid, Sergiy / Maymo Masip, Elsa / Megía Colet, Ana / VENDRELL FERRE, JOAN / Vendrell Ortega, Juan José
    Palabras clave: Women Proliferation Pai-1 Osteogenesis Neonatal adiposity Mesenchymal stromal cells Mellitus Insulin Human amniotic stem cells Glucose Gestational diabetes Gene-expression Disease Differentiation Cord blood insulin Angiogenesis
    Resumen: 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.
    Áreas temáticas: Odontología Molecular medicine Medicine, research & experimental Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Matemática / probabilidade e estatística Interdisciplinar Farmacia Engenharias iii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Cell biology Cell & tissue engineering Biotecnología Biochemistry, genetics and molecular biology (miscellaneous)
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: elsa.maymo@urv.cat monica.ballesteros@urv.cat sergiy.klidk@estudiants.urv.cat sergiy.klidk@estudiants.urv.cat ana.megia@urv.cat juanjose.vendrell@urv.cat
    Identificador del autor: 0000-0002-9133-3120 0000-0002-5101-9452 0000-0002-6994-6115
    Fecha de alta del registro: 2024-07-27
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02678-y
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Stem Cell Research & Therapy. 12 (1):
    Referencia de l'ítem segons les normes APA: Klid, Sergiy; Algaba-Chueca, Francisco; Maymo-Masip, Elsa; Guarque, Albert; Ballesteros, Monica; Diaz-Perdigones, Cristina; Gutierrez, Cristina; Vendr (2021). The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity. Stem Cell Research & Therapy, 12(1), -. DOI: 10.1186/s13287-021-02678-y
    DOI del artículo: 10.1186/s13287-021-02678-y
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2021
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry, Genetics and Molecular Biology (Miscellaneous),Cell & Tissue Engineering,Cell Biology,Medicine (Miscellaneous),Medicine, Research & Experimental,Molecular Medicine
    Women
    Proliferation
    Pai-1
    Osteogenesis
    Neonatal adiposity
    Mesenchymal stromal cells
    Mellitus
    Insulin
    Human amniotic stem cells
    Glucose
    Gestational diabetes
    Gene-expression
    Disease
    Differentiation
    Cord blood insulin
    Angiogenesis
    Odontología
    Molecular medicine
    Medicine, research & experimental
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Matemática / probabilidade e estatística
    Interdisciplinar
    Farmacia
    Engenharias iii
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciência de alimentos
    Cell biology
    Cell & tissue engineering
    Biotecnología
    Biochemistry, genetics and molecular biology (miscellaneous)
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