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

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.