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Gestational Diabetes-induced Changes to Amniotic Membrane MSCs May Impact Offspring

Review of “Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Fetal reprogramming has been proposed as a critical link between gestational diabetes mellitus (GDM) and long-term metabolic health consequences in offspring; however, the exact mechanisms at play remain relatively unknown. Interestingly, recent studies have revealed that GDM significantly impacts the proliferation [1], mitochondrial function [2], and angiogenesis [3] of human umbilical cord‐derived stem cells and these findings prompted researchers led by Sonia Fernández‐Veledo and Ana Megía (University Hospital of Tarragona Joan XXIII, Tarragona, Spain) to investigate the involvement of another placental stem cell type – mesenchymal stem cells derived from the amniotic membrane (AMSCs) [4]. 

Now, in their new STEM CELLS Translational Medicine article, Algaba‐Chueca et al. report that the maternal metabolism during gestation significantly influences AMSCs, suggesting that GDM may affect the health of offspring via these fetal precursor cells [5].

In summary, the authors conducted a prospective case‐control study that involved the isolation of AMSCs and resident macrophages from the placentas of pregnant women scheduled for a cesarean section that exhibited GDM or normal glucose tolerance. Initial analyses established that GDM-AMSCs displayed reduced proliferation and osteogenic potential and increased invasive and chemotactic capacity when compared to control AMSCs. 

Subsequent gene expression analyses revealed that GDM-AMSCs exhibited the deregulated expression of crucial inflammatory mediators associated with the development of insulin resistance, type 2 diabetes, obesity, and atherosclerosis [6]. At the same time, GDM-macrophages from the amniotic membrane also expressed high levels of pro-inflammatory gene expression. Importantly, control AMSCs exposed to a GDM-like environment (hyperglycemia, hyperinsulinemia, and palmitic acid [7]) in vitro displayed a similar phenotype to in vivo-derived GDM-AMSCs and, therefore, may represent a tractable in vitro model to decipher the disease mechanisms and test therapeutic approaches. 

Finally, and perhaps most significantly, the authors also discovered that the expression of genes related to the inflammatory response in AMSCs correlated to maternal insulin sensitivity, pre-pregnancy body mass index, and also fetal metabolic parameters, overall suggesting that GDM impacts fetal stem cells and this can induce metabolic dysfunction in offspring later in life. 

Overall, these fascinating findings support the hypothesis that maternal metabolism during gestation can reprogram metabolic parameters in offspring and identify a potentially crucial role for AMSCs; for all the new related studies, stay tuned to the Stem Cells Portal!


  1. Wajid N, Naseem R, Anwar SS, et al., The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells. Cell and Tissue Banking 2015;16:389-397.
  2. Kim J, Piao Y, Pak YK, et al., Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction. Stem Cells and Development 2014;24:575-586.
  3. Amrithraj AI, Kodali A, Nguyen L, et al., Gestational Diabetes Alters Functions in Offspring’s Umbilical Cord Cells With Implications for Cardiovascular Health. Endocrinology 2017;158:2102-2112.
  4. Parolini O and Caruso M, Review: Preclinical studies on placenta-derived cells and amniotic membrane: An update. Placenta 2011;32:S186-S195.
  5. Algaba-Chueca F, Maymó-Masip E, Ejarque M, et al., Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring. STEM CELLS Translational Medicine 2020;9:351-363.
  6. De Luca C and Olefsky JM, Inflammation and insulin resistance. FEBS Letters 2008;582:97-105.
  7. Kratz M, Coats Brittney R, Hisert Katherine B, et al., Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages. Cell Metabolism 2014;20:614-625.