Cytokine interplay among the diseased retina, inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy

Figure 1 The main mechanisms of the therapeutic effect of MSCs. MSC: Mesenchymal stem cell; HGF: Hepatocyte growth factor; IGF-1: Insulin-like growth factor-1; NGF: Nerve growth factor; VEGF: Vascular endothelial growth factor; TGF-β: Transforming growth factor-β; IDO: Indoleamine-2,3-dioxygenase; IL-6: Interleukin-6.

Figure 2 Expression of genes for immunoregulatory molecules and growth factors in the retina after intravitreal injection of pro-inflammatory cytokines. Mice were injected intravitreally with pro-inflammatory cytokines IL-lα, IFN-γ and TNF-α (10 ng of each, in a total volume of 4 μL), and the retinas from the control and treated eyes were harvested after 72 h. The expression of genes for IL-lα, IL-6, TNF-α and iNOS was determined in the retinas by real-time PCR.

Figure 3 Spontaneous and cytokine induced production of immunoregulatory cytokines and growth factors by mouse mesenchymal stem cells. Mouse mesenchymal stem cells (8 × 10⁴ cells in 1 mL of culture medium) were cultured for 48 h unstimulated (-) or in the presence of 10 ng/mL of IL-1β and TNF-α (Cyt.) The concentrations of IL-6, LIF, VEGF, IGF-I, HGF and CCL2 in supernatants were determined by ELISA. IL-6: Interleukin-6; LIF: Leukemia inhibitory factor; VEGF: Vascular endothelial growth factor; IGF-I: Insulin-like growth factor-I; HGF: hepatocyte growth factor.

Figure 4 The expression of genes for pro-inflammatory molecules in stimulated retinal explants and suppression of the gene expression by MSCs. Retinal explants were cultured for 48 h untreated (-), stimulated with IL-lα, IFN-γ and TNF-α (Cyt.) or stimulated with the cytokines in cultures containing MSCs (3 × 10⁴ in 1 mL). The expression of genes for IL-lα, IL-6 and iNOS in retinal explants was determined by real-time PCR. MSC: Mesenchymal stem cell; IL-6: Interleukin-6; IL-lα: Interleukin-lα; iNOS: Inducible nitrox oxide synthase; MSC: Mesenchymal stem cell.