BACKGROUND AIMS: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by an accelerated destruction of platelets as a result of the presence of autoreactive antibodies. Patients with ITP also display activated platelet-autoreactive T cells. Mesenchymal stem cells (MSC) inhibit both T- and B-cell activation and may have functional impairments in autoimmune disorders. METHODS: We analyzed the potential role of MSC in the pathogenesis of ITP. RESULTS: MSC from ITP showed an impaired proliferative capacity and a lower capability of inhibiting activated T-cell proliferation compared with healthy donors. While MSC from controls showed a decreased expression of p27 after stimulation with platelet-derived growth factor, this effect was not observed in MSC from patients. Furthermore, MSC from healthy donors down-regulated p16 upon exposure to platelet-released supernatant, while this effect was not observed for ITP. Interestingly, caspase 9 expression was higher in MSC from ITP. CONCLUSIONS: These abnormalities suggest a role of MSC malfunction in the physiopathology of the disease and may have therapeutic implications.
BACKGROUND AIMS: Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by an accelerated destruction of platelets as a result of the presence of autoreactive antibodies. Patients with ITP also display activated platelet-autoreactive T cells. Mesenchymal stem cells (MSC) inhibit both T- and B-cell activation and may have functional impairments in autoimmune disorders. METHODS: We analyzed the potential role of MSC in the pathogenesis of ITP. RESULTS: MSC from ITP showed an impaired proliferative capacity and a lower capability of inhibiting activated T-cell proliferation compared with healthy donors. While MSC from controls showed a decreased expression of p27 after stimulation with platelet-derived growth factor, this effect was not observed in MSC from patients. Furthermore, MSC from healthy donors down-regulated p16 upon exposure to platelet-released supernatant, while this effect was not observed for ITP. Interestingly, caspase 9 expression was higher in MSC from ITP. CONCLUSIONS: These abnormalities suggest a role of MSC malfunction in the physiopathology of the disease and may have therapeutic implications.
Authors: Jose A Pérez-Simon; Olga López-Villar; Enrique J Andreu; José Rifón; Sandra Muntion; María Diez Campelo; Fermín M Sánchez-Guijo; Carmen Martinez; David Valcarcel; Consuelo Del Cañizo Journal: Haematologica Date: 2011-03-10 Impact factor: 9.941
Authors: Marieke Roemeling-van Rhijn; Marlies E Reinders; Marcella Franquesa; Anja U Engela; Sander S Korevaar; Helene Roelofs; Paul G Genever; Jan Nm Ijzermans; Michiel Gh Betjes; Carla C Baan; Willem Weimar; Martin J Hoogduijn Journal: J Stem Cell Res Ther Date: 2013-12-12