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Oxidative stress plays a key role in the pathogenesis of numerous degenerative eye diseases. Mesenchymal stem cells (MSCs) have proven to be a promising cell therapeutic for these diseases. We investigated whether MSC-conditioned medium (MSC-CM) might provide a source of protective factors for retinal pigment epithelial cells (RPE) from oxidative stress-induced death. Primary human adult and fetal RPE cells were exposed to H(2)O(2). The death of RPE cells was analysed by measuring mitochondrial membrane potential and cell viability. RPE cells were cultured under serum-free conditions for 48 h, and the conditioned medium was incubated in the presence or absence of MSCs. Oxygen-glucose deprivation was performed in another group of cells after the conditioned medium was incubated in the presence or absence of Nrf2-siRNA. Cell viability and the induction of Nrf2, heme oxygenase-1 and erythropoietin were detected by MTT assay, RT-PCR and western blotting. We demonstrated that apoptosis-induced by oxidative stress (200 μmol/l H(2)O(2)) was attenuated in RPE cells treated with MSC-CM. The presence of MSCs in the medium enhanced Nrf2 transcription and protein expression, and treatment with Nrf2 siRNA reduced the cell protective effect induced by MSC-CM. Oxygen-glucose deprivation also increased the expression of Nrf2, heme oxygenase-1 and erythropoietin. The induction of these factors was attenuated after Nrf2 siRNA treatment. We showed that MSC-CM enhanced the antioxidant defense of RPE cells to protect them from oxidative stress-induced apoptosis. Therefore, MSC-CM can be used as a promising cell therapeutic for the treatment of oxidative stress-related degenerative eye diseases.Q:
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