Abstract
BackgroundGestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.MethodsHuman chorionic membrane-derived stem cells (CMSCs) were isolated from placentas of healthy and GDM pregnancies. Transcriptional profiling was performed by DNA microarray, and differentially regulated genes between GDM- and Healthy-CMSCs were used to analyse molecular functions, differentiation, and pathway enrichment. Altered genes and biological functions were validated via real-time PCR and in vitro assays.ResultsGDM-CMSCs displayed, vs. Healthy-CMSCs, 162 upregulated genes associated with increased migration ability, epithelial development, and growth factor-associated signal transduction while the 269 downregulated genes were strongly linked to angiogenesis and cellular metabolic processes. Notably, significantly reduced expression of detoxification enzymes belonging to the aldehyde dehydrogenase gene families (ALDH1A1/1A2, ALDH2, ALDH3) accounted for downregulation across several metabolic pathways. ALDH activity and inhibitor assays indicated that reduced gene expression of ALDHs affected ALDH enzymatic functions and resulted in oxidative stress dysregulation in GDM-CMSCs.ConclusionOur combined transcriptional analysis and in vitro functional characterisation have provided novel insights into fundamental biological differences in GDM- and Healthy-CMSCs. Enhanced mobility of GDM-CMSCs may promote MSC migration toward injured sites; however, impaired cellular metabolic activity may negatively affect any perceived benefit.
Highlights
Gestational diabetes (GDM) is a common complication of pregnancy
Identification of differentially expressed genes and biological function analysis Gene expression profiles of Chorionic membrane-derived stem cell (CMSC) derived from 3 healthy (H-CMSCs) and 3 Gestational diabetes mellitus (GDM) women (GDM-CMSCs) were determined by DNA microarray analysis
Applying a cutoff of p < 0.05 and 1.5-fold change between H-CMSCs and GDM-CMSCs, we identified a total of 431 differentially expressed genes (DEGs), including 162 upregulated and 269 downregulated genes in all 3 GDM samples (Fig. 1a)
Summary
Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and noninvasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. Mesenchymal stem cells (MSCs) are present in many adult tissues and play a role in tissue regeneration and maintenance. Their regenerative potential provides numerous benefits for disease treatment [1]. In terms of differentiation potential toward multiple lineages and their inherent immunomodulatory capacity, MSC from different tissues may share an element of a common transcriptional signature [2]. The MSC niche in specific adult tissues may affect and determine the gene expression in those specific tissue-derived MSCs [7]. An improved knowledge of MSC gene profiles would facilitate effective strategies for the use of MSCs in regeneration medicine
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