title: Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro.
abstract: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used to treat steroid-refractory acute graft-versus-host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs) and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs suppressed proliferation significantly in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of interferon (IFN)-γ and interleukin (IL)-17, whereas UCSCs and PVSCs promoted the production of IL-17 instead. Secretion of IL-10 was increased after addition of FMSCs and UCSCs. In this setting, BM-MSCs had no significant effect on secretion of IFN-γ, IL-17 or IL-10 in MLR cultures. When analysing the expression of adhesion markers, we noted that FMSCs expressed the highest levels of CD29 (β1), CD49d (α4) and CD54 (ICAM-1) compared to the other types of stromal cells. Thus, our data indicate that stromal cells isolated from term fetal membrane have great immunosuppressive capacity in terms of proliferation and production of proinflammatory cytokines from alloreactive T cells, and also promote anti-inflammatory IL-10. They express high levels of integrins that may be of importance in homing to inflamed tissues. Fetal membrane may provide a valuable source of cells with immunosuppressive properties and could possibly be used for treatment of acute GVHD and other inflammatory disorders.
authors.affiliation: Division of Clinical Immunology and Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden. helen.karlsson@ki.se
authors.forename: H
authors.initials: H
authors.lastname: Karlsson
authors.forename: T
authors.initials: T
authors.lastname: Erkers
authors.forename: S
authors.initials: S
authors.lastname: Nava
authors.forename: S
authors.initials: S
authors.lastname: Ruhm
authors.forename: M
authors.initials: M
authors.lastname: Westgren
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D002824:Chorionic Villi / Q000276:immunology; D005321:Extraembryonic Membranes / Q000166:cytology / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D007519:Isoantigens; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000276:immunology; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015815:Cell Adhesion Molecules; C508609:IL10 protein, human; D020381:Interleukin-17; D007519:Isoantigens; D016753:Interleukin-10; D007371:Interferon-gamma