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Mouse Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Perinatal Brain Injury Via a CD8+ T Cell Mechanism in a Model of Intrauterine Inflammation.

Authors
  • Zhao, Hongxi1
  • Xie, Li1
  • Clemens, Julia L1
  • Zong, Lu1
  • McLane, Michael W1
  • Arif, Hattan1
  • Feller, Mia C1
  • Jia, Bei1
  • Zhu, Yan1
  • Facciabene, Andreas2
  • Ozen, Maide3
  • Lei, Jun1
  • Burd, Irina4
  • 1 Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • 2 Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.
  • 3 Department of Pediatrics, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • 4 Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. [email protected]
Type
Published Article
Journal
Reproductive Sciences
Publisher
SAGE Publications
Publication Date
Jul 01, 2020
Volume
27
Issue
7
Pages
1465–1476
Identifiers
DOI: 10.1007/s43032-020-00157-y
PMID: 31997258
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The objective of this study was to determine if mouse bone marrow-derived mesenchymal stem cells (BMMSCs) ameliorate preterm birth and perinatal brain injury induced by intrauterine inflammation (IUI). A mouse model of IUI-induced perinatal brain injury at embryonic (E) day 17 was utilized. BMMSCs were derived from GFP-transgenic mice and phenotypically confirmed to be CD44+, Sca-1+, CD45-, CD34-, CD11b-, and CD11c- by flow cytometry and sorted by fluorescence-activated cell sorting (FACS). Dams were assigned to four groups: phosphate-buffered saline (PBS) + PBS, PBS + BMMSCs, lipopolysaccharide (LPS) + PBS, and LPS + BMMSCs. Following maternal IUI, there was a significant increase in CD8+ T cells in the placentas. Maternally administered BMMSCs trafficked to the fetal side of the placenta and resulted in significantly decreased placental CD8+ T cells. Furthermore, fetal trafficking of maternally administered BMMSCs correlated with an improved performance on offspring neurobehavioral testing in LPS + BMMSC group compared with LPS + PBS group. Our data support that maternal administration of BMMSCs can alleviate perinatal inflammation-induced brain injury and improve neurobehavioral outcomes in the offspring via CD8+ T cell immunomodulation at the feto-placental interface.

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