Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice

Decidual NK (dNK) cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as pre-eclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK) cells by a combination of hypoxia, TGF beta- 1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56 (Bright) idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56 (Dim) idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immu-nocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.