899 Effect of maternal serum on proliferation of the EndoC-ßH1 human beta cell line

Abstract

During pregnancy, the placenta secretes hormones that increase insulin resistance and raise blood glucose to support the growing fetus. To prevent maternal hyperglycemia, pregnancy is also associated with an increase in pancreatic beta cell mass. If molecular mechanisms that trigger maternal beta cell expansion can be determined, such pathways could be targeted for therapeutic beta cell regeneration. Exosomes, a type of extracellular vesicle, contain signaling molecules and are released by placental cells. Exosomes may be a source of inter-organ communication that signals beta cells to proliferate during pregnancy. Our purpose is to determine if exposure to maternal serum containing placental-derived exosomes triggers human beta cell proliferation. The genetically engineered human beta cell line EndoC-βH1 was used for this study because its phenotype and function are similar to primary human beta cells, and it proliferates reliably. EndoC-βH1 cells were cultured for one week in the presence of third trimester and postpartum serum drawn within 48 hours of delivery. We compared the maternal serum to serum from a male donor, fetal bovine serum, and serum-free conditions. Cell proliferation was measured using an EdU(5-ethynyl-2-deoxyuridine) assay. Six third trimester and postpartum donors were studied. Serum from three of six maternal donors induced a substantial (20-30%) increase in beta cell proliferation relative to serum-free conditions (Figure 1A). Of the three donors, five of six samples showed significant proliferation (p<0.05). (Figure 1A). Male human serum and fetal bovine serum only increased beta cell proliferation moderately (7-9%). We found no difference in the degree of beta-cell expansion induced when comparing serum samples collected during the third trimester and postpartum (Figure 1B). The results suggest a factor present in serum from 50% of pregnant donors triggers beta cells to proliferate. In future studies, we will deplete maternal serum of exosomes to determine whether the increased proliferation is attributable to maternal exosomes.