Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway
Mehdi Najar,
Saida Rahmani,
Wissam H. Faour,
Sami G. Alsabri,
Catherine A. Lombard,
Hussein Fayyad-Kazan,
Etienne M. Sokal,
Makram Merimi,
Hassan Fahmi
Affiliations
Mehdi Najar
Osteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC H2X 0A9, Canada
Saida Rahmani
LBBES Laboratory, Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco
Wissam H. Faour
Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos 5053, Lebanon
Sami G. Alsabri
Osteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC H2X 0A9, Canada
Catherine A. Lombard
Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Hussein Fayyad-Kazan
Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, P.O. Box 6573/14, Beirut 1103, Lebanon
Etienne M. Sokal
Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200 Brussels, Belgium
Makram Merimi
LBBES Laboratory, Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco
Hassan Fahmi
Osteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC H2X 0A9, Canada
As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs.
