Selenite Benefits Embryonic Stem Cells Therapy in Parkinson’s Disease

L.      -P. Tian; S.      Zhang; L.      Xu; W.      Li; Y.      Wang; S.      -D. Chen; J.      -Q. Ding

doi:10.2174/156652412802480880

Abstract

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.

Keywords: Cells transplantation, dopaminergic neurons, embryonic stem cells, inflammation, Parkinson’s disease, selenite, bradykinesia, neurodegenerative diseases, dopaminergic (DA) neurons, levodopa, transplantation, hypoxia, ischemia, oxidative stress, excitotoxicity.