title: Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.
abstract: Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells.
  
  
  CONCLUSIONS
  This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR.
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mandò
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Razini
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Novielli
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Gaia Maria
authors.initials: GM
authors.lastname: Anelli
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Belicchi
authors.affiliation: Ystem S.R.L., Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Erratico
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Banfi
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Meregalli
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tavelli
authors.affiliation: Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Baccarin
authors.affiliation: Department of Surgical Science, University of Turin, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rolfo
authors.affiliation: Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Motta
authors.affiliation: Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy UNISTEM Interdepartmental Centre for Stem Cell Research, Milan, Italy irene.cetin@unimi.it yvan.torrente@unimi.it.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Torrente
authors.affiliation: "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy Department of Mother and Child, Luigi Sacco Hospital, Milan, Italy irene.cetin@unimi.it yvan.torrente@unimi.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
mesh_terms: D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000473:pathology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology* / Q000502:physiology*; D055806:Microvessels / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000235:genetics; D010920:Placenta / Q000098:blood supply / Q000473:pathology*; D011247:Pregnancy
keywords: Intrauterine growth restriction; Mesenchymal stromal cells; Placenta; Pregnancy; Stem cells