Immunosuppressive properties of mesenchymal stem cells derived from bone marrow of patient with hematological malignant diseases

Abstract

Mesenchymal stem cells (MSCs) have received much attention because of their capabilities of differentiating into multiple mesenchymal lineages and supporting hematopoiesis. Recently, MSCs have gained further interests after the demonstration of an immunosuppressive role. However, it's still unclear whether the immunosuppressive capability of MSCs will be altered with disease state. In this study, our results showed that MSCs derived from patients with lymphoblastic leukemia (ALL), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) capable of suppressing the proliferation of T-lymphocyte stimulated in a mixed-lymphocyte reaction (MLR). The immunosuppressive effect of MSCs derived from ALL, HD and NHL on T-cell proliferation was dose-dependent. The supernatants of MSCs derived from ALL, HD and NHL had effect on T-cell proliferation. By using neutralising monoclonal antibodies, we found that transforming growth factor β1 (TGFβ1) and hepatocyte growth factor were major mediators of T-cell suppression by MSCs derived from ALL, HD and NHL. Although MSCs derived from patients with myelodysplastics syndromes (MDS) could inhibit T-cell proliferation stimulated with mitogen or in MLR, the inhibitory effect of MDS-MSCs was impaired. However, adherent cells derived from patients with acute myeloid leukemia (AML) showed abnormal immunomodulatory functions. Adherent cells derived from AML failed to suppress the proliferation of T-cell stimulated in MLR.

Keywords:

• Mesenchymal stem cells
• bone marrow
• hematological malignant diseases
• immunosuppressive effect