Keele Research Repository

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.