Chorionic and amniotic placental membrane-derived stem cells, from gestational diabetic women, have distinct insulin...

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.