Chorionic and amniotic placental membrane‐derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities

Chen, Liyun; Forsyth, Nicholas R.; Wu, Pensee

Abstract

Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.

Citation

Chen, L., Forsyth, N. R., & Wu, P. (2020). Chorionic and amniotic placental membrane‐derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities. Journal of Tissue Engineering and Regenerative Medicine, 14(2), 243-256. https://doi.org/10.1002/term.2988

• Journal Article Type: Article
• Acceptance Date: Oct 17, 2019
• Online Publication Date: Nov 14, 2019
• Publication Date: 2020-02
• Publicly Available Date: May 26, 2023
• Journal: Journal of Tissue Engineering and Regenerative Medicine
• Print ISSN: 1932-6254
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 2
• Pages: 243-256
• DOI: https://doi.org/10.1002/term.2988
• Keywords: cell differentiation; fetal stem cells; gestational diabetes; insulin-secreting cells; regenerative medicine
• Publisher URL: https://doi.org/10.1002/term.2988