Mesenchymal stem cells are functionally abnormal in patients with immune thrombocytopenic purpura

Cytotherapy. 2009;11(6):698-705. doi: 10.3109/14653240903051558.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Caspase 9 / immunology
  • Caspase 9 / metabolism*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p16 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p16 / immunology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism*
  • Middle Aged
  • Platelet-Derived Growth Factor / pharmacology
  • Purpura, Thrombocytopenic, Idiopathic / immunology
  • Purpura, Thrombocytopenic, Idiopathic / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Autoantibodies
  • Cyclin-Dependent Kinase Inhibitor p16
  • Platelet-Derived Growth Factor
  • Caspase 9