Tissues derived from reprogrammed Wharton's jelly stem cells of the umbilical cord as a platform to study gestational diabetes mellitus.

Abstract

Gestational diabetes mellitus (GDM) has been strongly associated with an increased risk of type 2 diabetes mellitus (T2DM) in later child and adulthood. The human umbilical cord and its contents are of fetal origin and represent the fetus genetically and physiologically. Since it is not possible to obtain tissues from the fetus and newborn to investigate the association between GDM and later T2DM, we reprogrammed the stem cells from the Wharton's jelly of umbilical cords (hWJSCs) of GDM and non-GDM mothers into induced pluripotent stem cells (iPSCs) and then differentiated the iPSCs into insulin-producing cells (IPCs) to provide pancreatic tissues that represent the fetus of GDM and normal mothers. These tissues are an attractive model to study the effects of glucose on the fetus. Interestingly, GDM-iPSCs had a decreased potential towards differentiation into IPCs. IPCs differentiated from GDM-iPSCs also had lower total insulin content and a lower capacity for insulin secretion to glucose stimulation compared to their normal-iPSC counterparts. This abnormal pathogenesis in GDM-iPSCs pancreatic differentiation recapitulates the pathology that may be observed in the infants of the diabetic mother (IDM) and while indicating adaptive mechanisms for fetal survival, may lead to the development of T2DM later in life. (199 words).