Current molecular medicine · 2012
Selenite benefits embryonic stem cells therapy in Parkinson's disease.
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Tian L-P, Zhang S, Xu L, Li W, Wang Y, Chen S-D, Ding J-Q
Аннотация
Embryonic stem cells (ESC) transplantation is a potential therapeutic approach for Parkinson's disease (PD). However, one of the main challenges to this therapy is the post-transplantation survival of dopaminergic (DA) neurons. In this study, mouse ESC were differentiated into DA neurons by a modified serum free protocol. These ESC-derived neurons were then transplanted into striatum of 6-OHDA lesioned rat. The viability of grafted DA neurons was decreased, accompanied by activated microglia and high levels of proinflammatory factors, such as TNF-α and iNOS, in the graft niche. This suggested that the local neuroinflammation might be involved in the reduced cells viability. Selenite, the source of essential micronutrient selenium, could inhibit NF-κB p65 nuclear translocation and subsequently reduce iNOS, COX-2 and TNF-α expression in LPS-treated BV2 cells in a dose dependant manner. Before the transplantation of ESC-derived DA neurons, 6-OHDA lesioned rats were intraperitoneally injected with selenite. The expression levels of TNF-α and iNOS were decreased by 30% and 50%, respectively, in selenite treated group. The survival of implanted DA neurons and the rotational behavior of transplanted rats were also remarkably improved by selenite treatment. To sum up, selenite might benefit ESCs transplantation therapy in PD through anti-inflammation effects.
Предметные рубрики MeSH
AnimalsAnti-Inflammatory AgentsCell Culture TechniquesCell DifferentiationCell SurvivalCells, CulturedCorpus StriatumCulture Media, Serum-FreeCyclooxygenase 2Dopaminergic NeuronsEmbryonic Stem CellsGraft SurvivalInflammationLipopolysaccharidesMaleMicrogliaNitric Oxide Synthase Type IIParkinson Disease, SecondaryRatsRats, Sprague-DawleySodium SeleniteTransplantation ToleranceTyrosine 3-Monooxygenase