Human mesenchymal stromal cells from adult and neonatal sources: a comparative in vitro analysis of their immunosuppressive properties against T cells

• Published in: Stem cells and development Vol. 23; no. 11; p. 1217
• Main Authors: Castro-Manrreza, Marta E, Mayani, Hector, Monroy-García, Alberto, Flores-Figueroa, Eugenia, Chávez-Rueda, Karina, Legorreta-Haquet, Victoria, Santiago-Osorio, Edelmiro, Montesinos, Juan José
• Format: Journal Article
• Language: English
• Published: United States 01-06-2014
• Subjects: Adult; Adult Stem Cells - cytology; Adult Stem Cells - immunology; Aging - physiology; Cell Separation; Cells, Cultured; Coculture Techniques; Humans; Immune Tolerance - physiology; Infant, Newborn; Lymphocyte Activation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - immunology; Primary Cell Culture; T-Lymphocytes - immunology
• ISSN: 1557-8534
• DOI: 10.1089/scd.2013.0363

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.