PURPOSE: The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP). METHODS: The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected. RESULTS: MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells. CONCLUSIONS: These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
PURPOSE: The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP). METHODS: The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected. RESULTS: MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells. CONCLUSIONS: These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
Authors: Joshua T Morgan; Heung Sun Kwon; Joshua A Wood; Dori L Borjesson; Stanislav I Tomarev; Christopher J Murphy; Paul Russell Journal: Exp Eye Res Date: 2015-02-24 Impact factor: 3.467
Authors: Erin A Kimbrel; Nicholas A Kouris; Gregory J Yavanian; Jianlin Chu; Yu Qin; Ann Chan; Ram P Singh; Deborah McCurdy; Lynn Gordon; Ralph D Levinson; Robert Lanza Journal: Stem Cells Dev Date: 2014-05-02 Impact factor: 3.272
Authors: Jong Joo Lee; Hyun Jeong Jeong; Mee Kum Kim; Won Ryang Wee; Won Woo Lee; Seung U Kim; Changmin Sung; Yung Hun Yang Journal: Purinergic Signal Date: 2013-09-17 Impact factor: 3.765