Chen, Liyun ORCID: https://orcid.org/0000-0003-1224-6262, Forsyth, NR ORCID: https://orcid.org/0000-0001-5156-4824 and Wu, P ORCID: https://orcid.org/0000-0003-0011-5636 (2019) 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). pp. 243-256.

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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.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Wiley at https://doi.org/10.1002/term.2988 - please refer to any applicable terms of use of the publisher. https://onlinelibrary.wiley.com/doi/full/10.1002/term.2988
Uncontrolled Keywords: cell differentiation; fetal stem cells; gestational diabetes; insulin-secreting cells; regenerative medicine
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: 07 Nov 2019 09:42
Last Modified: 02 Oct 2020 10:34
URI: https://eprints.keele.ac.uk/id/eprint/7152

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