title: Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.
abstract: The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia.
  
  
  METHODS
  Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs's cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent.
  
  
  RESULTS
  Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones.
  
  
  CONCLUSIONS
  Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia.
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy. rolfolab@gmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rolfo
authors.forename: Domenica
authors.initials: D
authors.lastname: Giuffrida
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Nuzzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Pierobon
authors.forename: Simona
authors.initials: S
authors.lastname: Cardaropoli
authors.forename: Ettore
authors.initials: E
authors.lastname: Piccoli
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.forename: Tullia
authors.initials: T
authors.lastname: Todros
mesh_terms: D015153:Blotting, Western; D006063:Chorionic Gonadotropin / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010920:Placenta / Q000166:cytology*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases