Chen, Liyun ORCID: https://orcid.org/0000-0003-1224-6262, Wang, C-T, Forsyth, NR ORCID: https://orcid.org/0000-0001-5156-4824 and Wu, P ORCID: https://orcid.org/0000-0003-0011-5636 (2020) Transcriptional profiling reveals altered biological characteristics of chorionic stem cells from women with gestational diabetes. Stem Cell Research & Therapy, 11 (1).

[img] Text
Chen et al_Revised Manuscript_SCRT_NRF290620.docx - Accepted Version

Download (138kB)
[img]
Preview
Text
Chen et al_Figures_011320.pdf - Supplemental Material

Download (1MB) | Preview
[img]
Preview
Text
s13287-020-01828-y.pdf - Published Version

Download (5MB) | Preview

Abstract

Background
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 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.

Methods
Human 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.

Results
GDM-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.

Conclusion
Our 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.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Uncontrolled Keywords: Aldehyde dehydrogenase, Chorionic stem cells, Gestational diabetes, Microarray analysis, Migration
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC660 Diabetes
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 31 Jul 2020 15:20
Last Modified: 31 Jul 2020 15:20
URI: https://eprints.keele.ac.uk/id/eprint/8466

Actions (login required)

View Item View Item