Mesenchymal stem cells ameliorate Th1-induced pre-eclampsia-like symptoms in mice via the suppression of TNF-α expression

PLoS One. 2014 Feb 18;9(2):e88036. doi: 10.1371/journal.pone.0088036. eCollection 2014.

Abstract

Pre-eclampsia (PE) is thought to be a pregnancy-induced autoimmune disease. Despite several strategies carried out for targeting specific factors relevant to its pathogenesis, PE remains potentially fatal to some patients. Here, we reported a way to isolate mesenchymal stem cells (MSCs) from decidua. The MSCs not only exhibited differentiation and self-renewal capacities, they also possessed immunomodulatory functions and secreted some soluble mediators including IL-6, TGF-β, IDO, VEGF and COX-2. Most importantly, the MSCs were specifically provided with the ability to suppress T cells proliferation by IDO in response to inflammatory cytokine IFN-γ. Moreover, we developed a Th1 cell-induced PE mouse model which displayed a high level of pathogenesis factor TNF-α. Strikingly, MSCs-based therapy significantly ameliorated both clinical and histopathological severity of PE symptoms including decreasing the blood pressure and proteinuria, suppressing glomerulonephritis, protecting the feto-placental development. The therapy also reversed abnormal TNF-α expression in uterine and splenic lymphocytes. These data suggest that MSCs may ameliorate Th1-induced PE-like symptoms in mice via the suppression of TNF-α and MSCs-based therapy may provide a potential novel method for PE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Animals
  • Blood Pressure
  • Cell Differentiation
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Glomerulonephritis / metabolism
  • Lymphocytes / cytology
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Osteogenesis
  • Pre-Eclampsia / pathology*
  • Pregnancy
  • Pregnancy, Animal
  • T-Lymphocytes / cytology
  • Th1 Cells / cytology*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Umbilical Cord / metabolism

Substances

  • Tumor Necrosis Factor-alpha

Grants and funding

This work supported by grants from the National Natural Science Foundation (project number: 81072410, 81270713), the Special Research Grant of Jiangsu Province Department of Health (project number: XK200709 and JHB2011-1) and Special grant for maternal-fetal medicine from Jiangsu province health department of China (project number: 81070508). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.