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PLoS One. 2016 Oct 13;11(10):e0164353. doi: 10.1371/journal.pone.0164353. eCollection 2016.

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

Author information

1
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
2
Gulbenkian Programme for Advanced Medical Education, Lisbon, Portugal.
3
Howard Hughes Medical Institute, Chevy Chase, MD, United States of America.
4
Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
5
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.

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, TGFß-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.

PMID:
27736914
PMCID:
PMC5063315
DOI:
10.1371/journal.pone.0164353
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

S.A.K. reports serving as a consultant to Roche, Siemens, Thermofisher and has financial interest in Aggamin Therapeutics. R.T. reports serving as a consultant to Roche, Thermofisher and has a financial interest in Aggamin Therapeutics. All other authors report no conflicts. S.A.K. is co-inventor on multiple patents (USPTO #7,740,849, #7,407,658, #7,335,362, #7,344,892) related to the use of angiogenic markers for the diagnosis, prediction and therapy of preeclampsia. R.T. is a co-inventor on a patent (USPTO #7,344,892) related to the use of angiogenic proteins for the prediction of preeclampsia. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

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