TY - JOUR
T1 - Mouse Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Perinatal Brain Injury Via a CD8+ T Cell Mechanism in a Model of Intrauterine Inflammation
AU - Zhao, Hongxi
AU - Xie, Li
AU - Clemens, Julia L.
AU - Zong, Lu
AU - McLane, Michael W.
AU - Arif, Hattan
AU - Feller, Mia C.
AU - Jia, Bei
AU - Zhu, Yan
AU - Facciabene, Andreas
AU - Ozen, Maide
AU - Lei, Jun
AU - Burd, Irina
N1 - Publisher Copyright:
© 2020, Society for Reproductive Investigation.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - CD8+ T cells
KW - Intrauterine inflammation
KW - Mesenchymal stem cells
KW - Perinatal brain injury
UR - http://www.scopus.com/inward/record.url?scp=85079592089&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079592089&partnerID=8YFLogxK
U2 - 10.1007/s43032-020-00157-y
DO - 10.1007/s43032-020-00157-y
M3 - Article
C2 - 31997258
AN - SCOPUS:85079592089
SN - 1933-7191
VL - 27
SP - 1465
EP - 1476
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 7
ER -