Stem cells have high potential for cell therapy in regenerative medicine. We previously isolated stem cell types from human amniotic fluid, derived from prenatal amniocentesis. One type, characterized by a fast doubling time, was designated as fast human amniotic stem cells (fHASCs). These cells exhibited high differentiation potential and immunoregulatory properties. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that influences stem-cell pluripotency, differentiation, mobility, and regulates immune functions. In this study, we investigated the influence of S1P on fHASC migration, proliferation, differentiation and immune regulatory functions. We found that fHASC stimulation with S1P potentiated their migratory and proliferative activity in vitro. Notably, short fHASC exposure to S1P enhanced their differentiation towards multiple lineages, including adipocytes, osteocytes and endothelial cells, an effect that was associated with downregulation of the main transcription factors involved in the maintenance of a stem-cell undifferentiated state. A specific crosstalk between S1P and tumor growth factor β1 (TGF-β1) has recently been demonstrated. We found that fHASC exposure to S1P in combination with TGF-β1 promoted the expression of the immune regulatory pathway of indoleamine 2,3-dioxygenase 1 (IDO1). In addition, human peripheral blood mononuclear cells, co-cultured with fHASCs treated with S1P and TGF-β1, expanded regulatory T-cells, via a mechanism requiring IDO1. Overall, this study demonstrates that S1P potentiates several properties in fHASCs, an effect that may be critical for exploiting the therapeutic potential of fHASCs and might explain the specific effects of S1P on stem cells during pregnancy.

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A cytochemical study was carried out on adenylate cyclase (AC) activity in the early human placenta. Samples of placental villi were incubated in a medium containing adenylyl-imidodiphosphate (AMP-PNP) as specific substrate. No AC reaction product was encountered in placenta villi taken at 5 and 7 weeks of pregnancy. AC activity appeared at 9 weeks. At 9 and 10 weeks, AC reaction product was localized on the basal plasma membranes and on apposed plasma membranes of the Langhans cytotrophoblast. At 11 weeks AC activity was also clearly visible on Langhans cytotrophoblast and syncytiotrophoblast apposed plasma membranes. No AC reaction product was ever detected on the syncytiotrophoblast microvillar membrane. These results are in agreement with biochemical studies that localize AC on the villous trophoblast plasma membranes associated with the fetal circulation.

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