Novel insights into the regulation of uterine vascular tone by sphingosine 1-phosphate

Abstract

s / Placenta 34 (2013) A1–A99 A3 stem cells in action. Vasculogenesis and angiogenesis of the fetal vasculature in the human placenta from mesenchymal stem cells and the sequential expression of endothelial adhesion molecules during vasculogenesis is a classic example of direct incorporation of stem cells in a growing vascular system. Modulation of the endothelial barrier and junctional phenotype with gestational age and altered maternal and placental milieu reflect paracrine repair and regeneration by vascular stem cells. Indeed, the phenotypic plasticity of the placental endothelial cells suggests their close proximity to the stem cell in the differentiation time line. This phenotypic plasticity has been successfully used by cell culture experimentalists for barrier studies. Moreover, de-differentiation of placental/umbilical cord derived endothelial cells in culture to a more mesenchymal/pericytic phenotype suggests that differentiation processes are not unidirectional. Recent studies of gene expression profiles of placental fetal endothelium combined with functional studies reporting an immature phenotype in the diabetic milieu further strengthen the stem cell but one nature and provide examples of endothelial de-differentiation in vivo. The phenotypic plasticity of fetal endothelial cells is advantageous to the fetus. It allows increased angiogenesis and permeability during gestation to sustain fetal growth; VEGF studies demonstrate this vividly. However, this very plasticity may then leave the fetus vulnerable to maternal diseases; the induced immature barrier phenotype or the accelerated aging upon sustained oxidative stress will lead to placental inefficiency and fetal morbidity. Fetal endothelial cells are not alone, other cell types in the placenta also show examples of plasticity and indeed trans-differentiation evidenced by differentiation of trophoblast cells during modulating of spiral arteries and expression of endothelial markers such as eNOS and caveolin-1. http://dx.doi.org/10.1016/j.placenta.2013.06.012 PL2.3. NOVEL INSIGHTS INTO THE REGULATION OF UTERINE VASCULAR TONE BY SPHINGOSINE 1-PHOSPHATE