1. Academic Validation
  2. The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity

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

  • Stem Cell Res Ther. 2021 Dec 20;12(1):608. doi: 10.1186/s13287-021-02678-y.
Sergiy Klid  # 1 2 Francisco Algaba-Chueca  # 3 2 Elsa Maymó-Masip 3 2 Albert Guarque 1 2 4 Mónica Ballesteros 1 2 4 Cristina Diaz-Perdigones 3 2 4 Cristina Gutierrez 1 3 2 Joan Vendrell 1 3 2 Ana Megía  # 5 6 7 Sonia Fernández-Veledo  # 8 9
Affiliations

Affiliations

  • 1 Rovira i Virgili University, Tarragona, Spain.
  • 2 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
  • 3 Department of Endocrinology and Nutrition, Research Unit, University Hospital of Tarragona Joan XXIII-Institut d´Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
  • 4 Department of Obstetrics and Gynecology, University Hospital of Tarragona Joan XXIII, Tarragona, Spain.
  • 5 Rovira i Virgili University, Tarragona, Spain. ana.megia@gmail.com.
  • 6 Department of Endocrinology and Nutrition, Research Unit, University Hospital of Tarragona Joan XXIII-Institut d´Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. ana.megia@gmail.com.
  • 7 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. ana.megia@gmail.com.
  • 8 Department of Endocrinology and Nutrition, Research Unit, University Hospital of Tarragona Joan XXIII-Institut d´Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. sonia.fernandezveledo@gmail.com.
  • 9 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. sonia.fernandezveledo@gmail.com.
  • # Contributed equally.
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.

Keywords

Angiogenesis; Cord blood insulin; Gestational diabetes; Human amniotic stem cells; Neonatal adiposity; PAI-1.

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