TY - JOUR
T1 - The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells
AU - Jones, Simon
AU - Horwood, Nicole
AU - Cope, Andrew
AU - Dazzi, Francesco
PY - 2007/9/1
Y1 - 2007/9/1
N2 - Although it has been widely demonstrated that human mesenchymal stem cells exert potent immunosuppressive effects, there is little information as to whether more mature mesenchymal stromal cells (SC) share the same property. Accordingly, we set out to test the ability of SC from different human tissues to inhibit the proliferation of PBMC following polyclonal stimuli. Chondrocytes, as well as fibroblasts from synovial joints, lung, and skin, were used as a source of SC. Irrespective of their differentiation potential and/or content of progenitor cells, SC from all tissues exhibited antiproliferative functions. This was in marked contrast to parenchymal cells. Although SC did not interfere with early T lymphocyte activation, they arrested stimulated T cells in the G0/G1 phase of the cell cycle and rescued them from apoptosis. In addition, IFN-γ and TNF-α production were reduced. We observed that the inhibitory effect is ultimately mediated by soluble factors, the production of which requires SC to be licensed in an inflammatory environment by cell contact. We conclude that the immunosuppressive effect of mesenchymal cells is not confined to multipotent stem cells, but is a fundamental characteristic of all stroma. Our data suggest that SC, appropriately licensed, regulate T cell homeostasis.
AB - Although it has been widely demonstrated that human mesenchymal stem cells exert potent immunosuppressive effects, there is little information as to whether more mature mesenchymal stromal cells (SC) share the same property. Accordingly, we set out to test the ability of SC from different human tissues to inhibit the proliferation of PBMC following polyclonal stimuli. Chondrocytes, as well as fibroblasts from synovial joints, lung, and skin, were used as a source of SC. Irrespective of their differentiation potential and/or content of progenitor cells, SC from all tissues exhibited antiproliferative functions. This was in marked contrast to parenchymal cells. Although SC did not interfere with early T lymphocyte activation, they arrested stimulated T cells in the G0/G1 phase of the cell cycle and rescued them from apoptosis. In addition, IFN-γ and TNF-α production were reduced. We observed that the inhibitory effect is ultimately mediated by soluble factors, the production of which requires SC to be licensed in an inflammatory environment by cell contact. We conclude that the immunosuppressive effect of mesenchymal cells is not confined to multipotent stem cells, but is a fundamental characteristic of all stroma. Our data suggest that SC, appropriately licensed, regulate T cell homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=38449121250&partnerID=8YFLogxK
M3 - Article
C2 - 17709496
AN - SCOPUS:38449121250
VL - 179
SP - 2824
EP - 2831
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -