Immunosuppressive properties of mesenchymal stem cells derived from bone marrow of patients with chronic myeloid leukemia.
Mesenchymal stem cells (MSCs) have emerged as excellent candidates for clinical application 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 is still unclear whether the immunosuppressive capability of MSCs will be altered with disease state. In this study, we obtained and expanded MSCs from bone marrow of patients with chronic myeloid leukemia (CML). Our results showed that MSCs derived from CML do not express costimulatory molecules CD40, CD80, and CD86. When MSCs derived from CML were added back to T cells stimulated by mitogens, a significant inhibition of T-cell proliferation was evident. MSCs differentiated into various mesenchymal lineages did not alter their immunosuppressive effect on T-cell proliferation. A significant T-cell inhibition was found in a transwell system, in which cell-cell contact between MSCs and effector cells was prevented. Furthermore, we found that transforming growth factor beta1 (TGF beta1) and hepatocyte growth factor (HGF) were major mediators of T-cell suppression by MSCs derived from CML. These results demonstrated that autologous MSCs derived from CML could effectively suppress T-cell proliferation.
Zhao
Zhi-Gang
ZG
Department of Hematology and Oncology, the Oncology Hospital of Tianjin Medical University, Tianjin, P.R. China.
Li
Wei-Ming
WM
Chen
Zhi-Chao
ZC
You
Yong
Y
Zou
Ping
P
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor