[Translate to Englisch:] Interferon-gamma and Tumor Necrosis Factor-alpha Differentially Affect Cytokine Expression and Migration Properties of Mesenchymal Stem Cells

[Translate to Englisch:] Hemeda H, Jakob M, Ludwig A , Giebel B , Lang S, Brandau S.
Stem Cells Dev.: 2010
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity to differentiate into different tissue cell types such as chondrocytes, osteocytes and adipocytes. In addition they can home to damaged, inflamed and malignant tissues and display immunomodulatory properties. Since tissue-derived factors might modulate these properties we decided to explore the impact of prototypic tissue-derived inflammatory cytokines such as TNF-alpha and IFN-gamma on immunomodulatory MSCs functions. To this end we used primary bone marrow and cord blood derived MSCs as well as an immortalized MSC line (V54/2) as model systems. We demonstrate that under unstimulated conditions, V54/2 cells constitutively express low levels of IDO, exert an immunosuppressive effect on activated T lymphocyte proliferation, secrete a distinct set of cytokines, and express a wide range of chemokine receptors. Upon stimulation, the proinflammatory cytokines IFN-gamma and TNF-alpha did not inhibit suppression of T cell proliferation, although IDO expression was upregulated by IFN-gamma. In contrast, TNF-alpha but not IFN-gamma amplified the cytokine production of V54/2 and primary MSCs. Interestingly, IFN-gamma was superior to TNF-alpha in upregulating expression of chemokine receptors and migration of the V54/2 cell line, while TNF-alpha was the predominant regulator of migration in primary MSCs. Altogether our data show that properties of MSCs depend on local environmental factors. In particular we have shown that IFN-gamma and TNF-alpha differentially regulate cytokine expression and migration of MSCs.