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

Hongxi Zhao, Li Xie, Julia L. Clemens, Lu Zong, Michael W. McLane, Hattan Arif, Mia C. Feller, Bei Jia, Yan Zhu, Andreas Facciabene, Maide Ozen, Jun Lei, Irina Burd

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1465-1476
Number of pages12
JournalReproductive Sciences
Volume27
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • CD8+ T cells
  • Intrauterine inflammation
  • Mesenchymal stem cells
  • Perinatal brain injury

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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