cellmedicine
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A neat paper I found today that describes some of the molecular mechanisms by which stem cells of the mesenchymal type inhibit the pathological immune response in rheumatoid arthritis. See thats the neat thing about mesenchymal stem cells, on the one hand the suppress pathological immune responses but on the other hand they stimulate regeneration of different tissues.
Rheumatology (Oxford). 2008 Jan;47(1):22-30.
Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis.Zheng ZH, Li XY, Ding J, Jia JF, Zhu P.
Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi?an 710032, Shaanxi Province, China. zhuping@fmmu.edu.cn.
Objective. Rheumatoid arthritis (RA) is a T-cell-mediated systematic disease and is usually accompanied by articular cartilage damage. In the present study, we explored the effects of bone marrow-derived mesenchymal stem cells (MSCs) and MSC-differentiated chondrocytes (MSC-chondrocytes) on the responses of antigen-specific T cells in RA to type II collagen (CII) to evaluate the potential therapeutic value of MSCs in RA treatment. Methods. The effects of both MSCs and MSC-chondrocytes on the proliferation, activation-antigen expression (CD69 and CD25) and cytokine production [interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-4] of CII-reactive T cells in RA patients were investigated with the stimulation of CII or otherwise. CD3/annexin V staining was used to evaluate T-cell apoptosis in the inhibition. The role of transforming growth factor-beta1 (TGF-beta1) underlying the inhibition was also investigated. Results. MSCs failed to elicit positive responses of CII-reactive T cells, whereas they significantly suppressed CII-stimulated T-cell proliferation and activation-antigen expression in a dose-dependent fashion without inducing T-cell apoptosis. The inhibition was observed even after MSCs were added as late as 3 days after the initiation of stimulation. Moreover, MSCs inhibited both CD4(+) and CD8(+) T cells from producing IFN-gamma and TNF-alpha, while they up-regulated the levels of IL-10 and restored the secretion of IL-4. TGF-beta1 was confirmed to play a critical role in the inhibition. Throughout our study, MSC-chondrocytes shared similar properties with MSCs. Conclusion. Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.
Rheumatology (Oxford). 2008 Jan;47(1):22-30.
Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis.Zheng ZH, Li XY, Ding J, Jia JF, Zhu P.
Department of Clinical Immunology, State key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi?an 710032, Shaanxi Province, China. zhuping@fmmu.edu.cn.
Objective. Rheumatoid arthritis (RA) is a T-cell-mediated systematic disease and is usually accompanied by articular cartilage damage. In the present study, we explored the effects of bone marrow-derived mesenchymal stem cells (MSCs) and MSC-differentiated chondrocytes (MSC-chondrocytes) on the responses of antigen-specific T cells in RA to type II collagen (CII) to evaluate the potential therapeutic value of MSCs in RA treatment. Methods. The effects of both MSCs and MSC-chondrocytes on the proliferation, activation-antigen expression (CD69 and CD25) and cytokine production [interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-10 and IL-4] of CII-reactive T cells in RA patients were investigated with the stimulation of CII or otherwise. CD3/annexin V staining was used to evaluate T-cell apoptosis in the inhibition. The role of transforming growth factor-beta1 (TGF-beta1) underlying the inhibition was also investigated. Results. MSCs failed to elicit positive responses of CII-reactive T cells, whereas they significantly suppressed CII-stimulated T-cell proliferation and activation-antigen expression in a dose-dependent fashion without inducing T-cell apoptosis. The inhibition was observed even after MSCs were added as late as 3 days after the initiation of stimulation. Moreover, MSCs inhibited both CD4(+) and CD8(+) T cells from producing IFN-gamma and TNF-alpha, while they up-regulated the levels of IL-10 and restored the secretion of IL-4. TGF-beta1 was confirmed to play a critical role in the inhibition. Throughout our study, MSC-chondrocytes shared similar properties with MSCs. Conclusion. Both MSCs and MSC-chondrocytes suppressed CII-reactive T-cell responses to CII in RA, which suggested that MSCs could be a potential candidate for RA treatment in future if further confirmed in vivo.