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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

Authors

Liyun Chen

Nicholas R. Forsyth



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.

Journal Article Type Article
Acceptance Date Oct 17, 2019
Online Publication Date Nov 14, 2019
Publication Date 2020-02
Publicly Available Date Mar 29, 2024
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

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