Mesenchymal stem cells are functionally abnormal in patients with immune thrombocytopenic purpura.
OBJECTIVE
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.
Pérez-Simón
Jose Antonio
JA
Servicio de Hematología, Hospital Clínico Universitario y Centro de Investigación del Cáncer de Salamanca, Spain. pesimop@usal.es
Tabera
Soraya
S
Sarasquete
María Eugenia
ME
Díez-Campelo
María
M
Canchado
Javier
J
Sánchez-Abarca
Luis Ignacio
LI
Blanco
Belén
B
Alberca
Ignacio
I
Herrero-Sánchez
Carmen
C
Cañizo
Consuelo
C
San Miguel
Jesús F
JF
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D053453:Caspase 9 / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D001323:Autoantibodies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010982:Platelet-Derived Growth Factor; D053453:Caspase 9