2. Academic Validation
  3. The protective mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against neutrophil extracellular trap-induced placental damage

The protective mechanism of human umbilical cord mesenchymal stem cell-derived exosomes against neutrophil extracellular trap-induced placental damage

  • Placenta. 2024 Aug:153:59-74. doi: 10.1016/j.placenta.2024.05.136.
Yuan Wang 1,  Qingfeng Lv 1,  Jing Li 2,  Min Hu 3,  Hao Li 4,  Meihua Zhang 4,  Di Shen 5,  Xietong Wang 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Street, Jinan, Shandong, 250021, China.
  • 2 Department of Pediatrics, Central Hospital Affiliated to Shandong First Medical University, China.
  • 3 Center for Reproductive Medicine, Shandong University, Jinan, Shandong, 250012, China.
  • 4 Department of Obstetrics and Gynecology, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
  • 5 Department of Obstetrics and Gynecology, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China. Electronic address: cindy871119@163.com.
  • 6 Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Street, Jinan, Shandong, 250021, China; Department of Obstetrics and Gynecology, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China. Electronic address: wxt65@vip.163.com.
PMID: 38823320 DOI: 10.1016/j.placenta.2024.05.136
Abstract

Introduction: Preeclampsia (PE) is a pregnancy-specific complication. Its etiology and pathogenesis remain unclear. Previous studies have shown that neutrophil extracellular traps (NETs) cause placental dysfunction and lead to PE. Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) have been widely used to treat different diseases. We investigated whether hUCMSC-EXOs can protect against NET-induced placental damage.

Methods: NETs were detected in the placenta by immunofluorescence. The impact of NETs on cellular function and the effect of hUCMSC-EXOs on NET-induced placental damage were evaluated by 5-ethynyl-20-deoxyuridine (EdU) cell proliferation, Lactate Dehydrogenase (LDH), Reactive Oxygen Species (ROS), and cell migration, invasion and tube formation assays; flow cytometry; and Western blotting.

Results: The number of placental NETs was increased in PE patients compared with control individuals. NETs impaired the function of endothelial cells and trophoblasts. These effects were partially reversed after N-acetyl-L-cysteine (NAC; ROS inhibitor) or DNase I (NET lysing agent) pretreatment. HUCMSC-EXOs ameliorated NET-induced functional impairment of endothelial cells and trophoblasts in vitro, partially reversed NET-induced inhibition of endothelial cell and trophoblast proliferation, and partially restored trophoblast migration and invasion and endothelial cell tube formation. Exosomes inhibited ROS production in these two cell types, suppressed p38 mitogen-activated protein kinase (p38 MAPK) signaling activation, activated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, and modulated the Bax, Bim, Bcl-2 and cleaved Caspase-3 levels to inhibit Apoptosis.

Discussion: HUCMSC-EXOs can reverse NET-induced placental endothelial cell and trophoblast damage, possibly constituting a theoretical basis for the treatment of PE with exosomes.

Keywords

Apoptosis; Exosome; Neutrophil extracellular trap; Preeclampsia; ROS.

Figures
Products