title: Human mesenchymal stromal cells from adult and neonatal sources: a comparative in vitro analysis of their immunosuppressive properties against T cells.
abstract: Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM-the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3(+) T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BM-MSCs and UCB-MSCs significantly inhibited the proliferation of both CD4(+) and CD8(+) activated T cells in a cell-cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-γ, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4(+)CD25(+)CTLA-4(+). Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications.
authors.affiliation: 1 Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center , IMSS, Mexico City, Mexico .
authors.forename: Marta E
authors.initials: ME
authors.lastname: Castro-Manrreza
authors.forename: Hector
authors.initials: H
authors.lastname: Mayani
authors.forename: Alberto
authors.initials: A
authors.lastname: Monroy-García
authors.forename: Eugenia
authors.initials: E
authors.lastname: Flores-Figueroa
authors.forename: Karina
authors.initials: K
authors.lastname: Chávez-Rueda
authors.forename: Victoria
authors.initials: V
authors.lastname: Legorreta-Haquet
authors.forename: Edelmiro
authors.initials: E
authors.lastname: Santiago-Osorio
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Montesinos
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000276:immunology; D000375:Aging / Q000502:physiology*; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D061251:Primary Cell Culture; D013601:T-Lymphocytes / Q000276:immunology*