Selenite benefits embryonic stem cells therapy in Parkinson's disease.
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.
Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
L-P
LP
Tian
S
S
Zhang
L
L
Xu
W
W
Li
Y
Y
Wang
S-D
SD
Chen
J-Q
JQ
Ding
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016895:Culture Media, Serum-Free; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000201:enzymology / Q000637:transplantation*; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D006085:Graft Survival / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018038:Sodium Selenite / Q000627:therapeutic use*; D023001:Transplantation Tolerance / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016895:Culture Media, Serum-Free; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D014446:Tyrosine 3-Monooxygenase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D018038:Sodium Selenite