Submitted on May 2, 2006
Accepted on October 20, 2006
Tissue-Specific Stem Cells
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Chondrogenic-differentiation Alters the Immunosuppressive Property of Bone Marrow-derived Mesenchymal Stem Cells and the Effect Is Partially Due to the Up-regulated Expression of B7 Molecules
Xi Chen 1,
Angela McClurg 2,
Guang-Qian Zhou 3,
Mervyn McCaigue 1,
Marilyn Ann Armstrong 2,
Gang Li 1*
1 Department of Orthopaedic Surgery, Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom
2 Department of Immunology, Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom
3 Department of Surgery, Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom
* To whom correspondence should be addressed. E-mail: g.li{at}qub.ac.uk.
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Abstract |
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To investigate the immunosuppressive properties of mesenchymal stem cells (MSCs), in the present study we examined the immunogenicity of undifferentiated and tri-lineage (chondrocytes, osteoblasts and adipocytes) differentiated rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic-differentiation, rat bone marrow-derived MSCs stimulated human peripheral blood monocyte-derived DCs (hDCs), leading to 8- and 4-fold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The Chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs inrosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDCs maturation causing higher CD83 expression in hDCs, whereas undifferentiated MSCs, osteogenic-and adipogenic-differentiated MSCs showed inhibitory effect on hDCs maturation. The co-stimulatory molecules B7 were up-regulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of co-cultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of DCs. The up-regulated expression of B7 molecules on the chondrogenic differentiated MSCs may be partially responsible for this event.
Key Words.
MSCs, immunogenicity, chondrogenic-differentiation, DCs
