title: Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta.
abstract: Mesenchymal stromal cells (MSCs) are a promising tool in cell therapies because of their multipotent, bystander, and immunomodulatory properties. Although bone marrow represents the main source of MSCs, there remains a need to identify a stem cell source that is safe and easily accessible and yields large numbers of cells without provoking debates over ethics. In this study, MSCs isolated from amniotic fluid and placenta were compared with bone marrow MSCs. Their immunomodulatory properties were studied in total activated T cells (peripheral blood mononuclear cells) stimulated with phytohemagglutinin (PHA-PBMCs). In particular, an in vitro co-culture system was established to study: (i) the effect on T-lymphocyte proliferation; (ii) the presence of T regulatory lymphocytes (Treg); (iii) the immunophenotype of various T subsets (Th1 and Th2 naïve, memory, effector lymphocytes); (iv) cytokine release and master gene expression to verify Th1, Th2, and Th17 polarization; and (v) IDO production. Under all co-culture conditions with PHA-PBMCs and MSCs (independently of tissue origin), data revealed: (i) T proliferation inhibition; (ii) increase in naïve T and decrease in memory T cells; (iii) increase in T regulatory lymphocytes; (iv) strong Th2 polarization associated with increased interleukin-10 and interleukin-4 levels, Th1 inhibition (significant decreases in interleukin-2, tumor necrosis factor-α, interferon-γ, and interleukin-12) and Th17 induction (production of high concentrations of interleukins-6 and -17); (v) indoleamine-2,3-dioxygenase mRNA induction in MSCs co-cultured with PHA-PBMCs. AF-MSCs had a more potent immunomodulatory effect on T cells than BM-MSCs, only slightly higher than that of placenta MSCs. This study indicates that MSCs isolated from fetal tissues may be considered a good alternative to BM-MSCs for clinical applications.
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy; Department of Public Health and Pediatrics, University of Turin, Turin, Italy. Electronic address: katia.mareschi@unito.it.
authors.forename: Katia
authors.initials: K
authors.lastname: Mareschi
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglia
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Sanavio
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Rustichelli
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Muraro
authors.affiliation: Clinical Biochemistry Laboratory, University Hospital City of Science and Health of Turin, San Giovanni Battista's Hospital, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Defedele
authors.affiliation: Department of Public Health and Pediatrics, University of Turin, Turin, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Bergallo
authors.affiliation: Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, University Hospital City of Science and Health of Turin, Regina Margherita Children's Hospital, Turin, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines