Author, as appears in the article.: Klid, Sergiy; Algaba-Chueca, Francisco; Maymo-Masip, Elsa; Guarque, Albert; Ballesteros, Monica; Diaz-Perdigones, Cristina; Gutierrez, Cristina; Vendrell, Joan; Megia, Ana; Fernandez-Veledo, Sonia;
Department: Bioquímica i Biotecnologia Medicina i Cirurgia
URV's Author/s: Ballesteros Pérez, Monica / GUTIÉRREZ FORNÉS, CRISTINA / Klid Klid, Sergiy / Maymo Masip, Elsa / Megía Colet, Ana / VENDRELL FERRE, JOAN / Vendrell Ortega, Juan José
Keywords: 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
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.
Thematic Areas: 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)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: 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
Author identifier: 0000-0002-9133-3120 0000-0002-5101-9452 0000-0002-6994-6115
Record's date: 2024-07-27
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Stem Cell Research & Therapy. 12 (1):
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
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV