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

• Type of Material: Article
• Authors: Ricardo C. Cavalli, Harvard Medical School; Ana Sofia Cerdeira, Harvard Medical School; Elizabeth Perniconel, Harvard Medical School; Henri A. Korkes, Harvard Medical School; Suzanne D. Burke, Harvard Medical School; Augustine Rajakumar, Emory University; Ravi I. Thadhani, Harvard Medical School; Drucilla J. Roberts, Harvard Medical School; Manoj Bhasinl, Harvard Medical School; S. Ananth Karumanchi, Harvard Medical School; Hernan D. Kopcow, Harvard Medical School
• Language: English
• Date: 2016-10-13
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Cavalli et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0164353
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 10
• Start Page: e0164353
• End Page: e0164353
• Grant/Funding Information: This project was funded by the American Heart Association (http://www.heart.org) Grant in Aid 13GRNT17070111 to HDK, Preeclampsia Foundation (http://www.preeclampsia.org) Vision Grant to ASC, Howard Hughes Medical Institute (http://www.hhmi.org) to SAK, FAPESP Sao Paulo Research Foundation (http://www.fapesp.br/en/) to RCC, CAPES Foundation (http://www.capes.gov.br) to HAK.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: UTERINE ARTERY DOPPLER; GROWTH RESTRICTION; Multidisciplinary Sciences; TROPHOBLAST INVASION; EARLY-PREGNANCY; NATURAL-KILLER-CELLS; Science & Technology; PLACENTAL BED; Science & Technology - Other Topics; BLOOD-FLOW; INTERFERON-GAMMA; COLONY-STIMULATING FACTOR; METRIAL GLAND-CELLS
• Research Categories: Health Sciences, Pathology

Abstract

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 preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK) cells by a combination of hypoxia, TGFβ-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 CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.