The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity.
Angiogenesis
Cord blood insulin
Gestational diabetes
Human amniotic stem cells
Neonatal adiposity
PAI-1
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
20 12 2021
20 12 2021
Historique:
received:
22
03
2021
accepted:
09
12
2021
entrez:
21
12
2021
pubmed:
22
12
2021
medline:
24
3
2022
Statut:
epublish
Résumé
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). 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 34930438
doi: 10.1186/s13287-021-02678-y
pii: 10.1186/s13287-021-02678-y
pmc: PMC8691045
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
608Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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