title: Mesenchymal stromal cells and immunomodulation: A gathering of regulatory immune cells.
abstract: Because of their well-recognized immunomodulatory properties, mesenchymal stromal cells (MSCs) represent an attractive cell population for therapeutic purposes. In particular, there is growing interest in the use of MSCs as cellular immunotherapeutics for tolerance induction in allogeneic transplantations and the treatment of autoimmune diseases. However, multiple mechanisms have been identified to mediate the immunomodulatory effects of MSCs, sometimes with several ambiguities and inconsistencies. Although published studies have mainly reported the role of soluble factors, we believe that a sizeable cellular component plays a critical role in MSC immunomodulation. We refer to these cells as regulatory immune cells, which are generated from both the innate and adaptive responses after co-culture with MSCs. In this review, we discuss the nature and role of these immune regulatory cells as well as the role of different mediators, and, in particular, regulatory immune cell induction by MSCs through interleukin-10. Once induced, immune regulatory cells accumulate and converge their regulatory pathways to create a tolerogenic environment conducive for immunomodulation. Thus, a better understanding of these regulatory immune cells, in terms of how they can be optimally manipulated and induced, would be suitable for improving MSC-based immunomodulatory therapeutic strategies.
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium. Electronic address: mnajar@ulb.ac.be.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Gordana
authors.initials: G
authors.lastname: Raicevic
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Hussein
authors.initials: H
authors.lastname: Fayyad-Kazan
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Toungouz
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D001327:Autoimmune Diseases; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors; D056747:Immunomodulation / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C508609:IL10 protein, human; D007155:Immunologic Factors; D016753:Interleukin-10
keywords: MSCs; immunomodulation; regulatory immune cells; tolerance